Drugs of Today 2014, 50(1): 51-100copyright © 2014 Prous science, s.a.u. or its licensors. all rights reserved. ccc: 1699-3993/2014 DoI: 10.1358/dot.2014.50.1.2116673 REVIEW ThE YEaR’s NEW DRugs & BIologIcs, 2013: PaRT I A.I. Graul, E. Cruces and M. Stringer Thomson Reuters, Barcelona, spain CONTENTS summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 agents for analgesia & anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Psychopharmacological drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Neurologic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Respiratory drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 cardiovascular drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Renal–urologic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 hematologic agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Endocrine drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Dermatologic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 gastrointestinal agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 anti-infective therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Therapy of musculoskeletal & connective tissue diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Immunomodulators & agents for immunization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Treatment of cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ophthalmic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Metabolic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Treatment of poisoning & drug dependency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Dental agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Diagnostic agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Correspondence: a.I. graul, Thomson Reuters, Barcelona, spain. E-mail:
[email protected]. 51 ThE YEaR’s NEW DRugs & BIologIcs 2013 A.I. Graul et al. SUMMARY This article provides a comprehensive overview of the 56 new drugs and biologics introduced for the first time in 2013, the largest number in at least a decade. This includes 20 new orphan drugs and 10 first-in-class agents, as well as the first three products bearing the FDA’s new Breakthrough Therapy Designation. The review also covers 30 important new line extensions, encompassing new indications, new formulations and new combinations of previously marketed agents. In addition to this bumper crop of new launches, another 19 products were approved for the first time during the year but not yet launched by the close of this article; these new products are also discussed. agents, defined as drugs with a new and unique mechanism of action. also launched this year were 30 important new line extensions (new indications, new formulations or new combinations of previously marketed drugs and biologics). The most active therapeutic group for new drugs and biologics in 2013 was oncolytic drugs, with 12 new drugs and biologics reaching the market to treat patients with cancer, followed by immunologic agents and metabolic drugs, with 11 and 7 products, respectively (see Table I). INTRODUCTION Twenty of the new products and line extensions introduced in 2013 have orphan drug status, also a much higher number than previous years, reflecting the recent upsurge of R&D investment in this area. In another exciting new development, the first three products bearing the FDa’s new Breakthrough Therapy Designation were approved for marketing by the agency. The year 2013 witnessed the first launches of 56 new drugs and biologics, the highest number in at least a decade (see Table I). This includes 10 first-in-class as shown in Figure 1, the united states was by far the most important market for new drugs, with 42 global first launches in 2013 taking place in that country. Japan Key words: New drug launches – New biologics – New approvals – line extensions – orphan drugs Table I. Drugs & biologics introductions by therapeutic category, 2003-2013. Therapeutics 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 central nervous system 3 6 6 1 3 4 7 4 5 2 4 Respiratory 3 0 1 0 2 2 2 1 1 2 1 cardiovascular 1 0 2 2 2 2 1 1 1 1 2 Renal–urologic 3 2 3 3 1 2 2 0 2 1 0 hematologic 1 1 1 0 2 6 3 1 3 2 1 gastrointestinal 0 0 1 2 1 3 1 1 0 1 4 Endocrine drugs 1 2 3 3 2 0 3 2 1 4 4 Dermatologic 2 0 0 0 0 2 1 0 1 2 1 anti-infective 5 1 6 2 5 3 1 2 6 0 5 antiarthritic 1 0 0 1 0 1 3 0 1 2 0 Immunologic 2 2 6 9 4 3 17 5 4 5 11 cancer 3 7 6 7 5 1 6 7 7 10 12 ophthalmic 0 0 2 2 0 1 1 1 2 0 1 Metabolic drugs 4 2 1 7 2 2 3 4 2 2 7 Poisoning & drug abuse 0 0 1 1 0 0 0 0 0 1 1 Dental 0 0 1 0 0 0 0 0 0 0 1 Diagnostic agents 0 3 2 1 1 1 0 0 0 1 1 Total 29 26 42 41 30 33 51 29 36 36 56 52 ThoMsoN REuTERs – Drugs of Today 2014, 50(1) A.I. Graul et al. ThE YEaR’s NEW DRugs & BIologIcs 2013 agency (DEa) schedule II drug. Zogenix plans to launch it during the first quarter of 2014. usa Japan Eu India canada argentina Figure 1. Distribution of new launches in 2013 by country. followed with 5, while India debuted in this listing with 4 new launches. In addition to this bumper crop of new launches, another 19 products were approved for the first time during the year but not yet launched by the close of this article; this number includes both new drugs and biologics, as well as important new line extensions. The information in this review and the accompanying tables was compiled from company communications, Thomson Reuters Drug News and the Thomson Reuters IntegritysM and Thomson Reuters cortellis™ drug databases. AGENTS FOR ANALGESIA & ANESTHESIA The long-acting opioid analgesic hydrocodone bitartrate (Zohydro™ ER; Zogenix) was approved for the first time last year in the u.s., where it is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Zohydro ER is the first extended-release hydrocodone therapy that is formulated without acetaminophen. acetaminophen overdose is a leading cause of acute liver failure in the u.s., and 63% of unintentional acetaminophen overdoses are attributed to the use of hydrocodoneacetaminophen combination products such as Vicodin®. Zohydro uses alkermes’ patented spheroidal oral Drug absorption system (soDas®) drug delivery technology. The product will be classified as a Drug Enforcement ThoMsoN REuTERs – Drugs of Today 2014, 50(1) In March, the u.K.’s Medicines and healthcare products Regulatory agency (MhRa) approved horizon Pharma’s Duexis® (ibuprofen/famotidine) for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in patients who require regular treatment with high-dose ibuprofen administered three times a day and who are at risk of developing nonsteroidal anti-inflammatory drug (NsaID)-associated gastric and/or duodenal ulcers. horizon Pharma is seeking a commercial partner or partners for Duexis in the u.K. and the rest of Europe. Duexis, a proprietary singletablet combination of the NsaID ibuprofen and the histamine h2 receptor antagonist famotidine, is indicated in the u.s. for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers in patients who are taking ibuprofen for those indications. The u.K. approval was the first worldwide to include the new indication of ankylosing spondylitis. NuPathe’s Zecuity™, an iontophoretic transdermal system for delivery of the 5-hT1B/1D receptor agonist sumatriptan, was approved last year in the u.s. for the acute treatment of migraine with or without aura in adults. Zecuity is a single-use, battery-powered patch that is applied to the upper arm or thigh during a migraine. Following application and with a press of a button, Zecuity initiates transdermal delivery, bypassing the gastrointestinal tract. Throughout the 4-hour dosing period, the microprocessor within Zecuity continuously monitors skin resistance and adjusts drug delivery accordingly to ensure delivery of 6.5 mg of sumatriptan, with minimal patient-to-patient variability. The product provides relief of both migraine headache pain and migraine-related nausea. NuPathe is currently seeking partnerships to maximize the commercial potential of Zecuity, and has delayed product launch until the identification of said commercial partner. PSYCHOPHARMACOLOGICAL DRUGS a new treatment for major depressive disorder (MDD) was approved in the u.s. in July 2013: Pierre Fabre and Forest’s levomilnacipran (Fetzima™), a once-daily serotonin and norepinephrine reuptake inhibitor (sNRI) and the active isomer of the marketed antidepressant milnacipran. The NDa was supported by three double-blind phase III studies including two fixed-dose studies, and one flexible-dose study that compared levomilnacipran 53 ThE YEaR’s NEW DRugs & BIologIcs 2013 to placebo in adults with MDD. combined, these studies included a total of more than 1,600 adult patients who received a once-daily dose of either levomilnacipran (40, 80 or 120 mg) or placebo. In each study, the primary endpoint was change from baseline to endpoint in the Montgomery-Åsberg Depression Rating scale total score and the secondary endpoint was change from baseline to endpoint in the sheehan Disability scale total score. In all three studies, statistically significant improvement was seen for the levomilnacipran group compared with placebo on both the primary and secondary endpoints. The product was launched in the u.s., its first market, in December 2013. The serotonergic agent vortioxetine (Brintellix™; lundbeck/Takeda) was approved by the u.s. Food and Drug administration (FDa) in september 2013 for the treatment of MDD. Vortioxetine inhibits serotonin reuptake and acts as a 5-hT1a receptor agonist, 5-hT1B partial agonist and 5-hT3, 5-hT1D and 5-hT7 receptor antagonist. This multifaceted profile results in the modulation of neurotransmission in several systems, including predominantly serotonin, but conceivably also the norepinephrine, dopamine, histamine, acetylcholine, gaBa and glutamate systems. The relative contribution of each individual mechanism of action has not been established. Vortioxetine is the first antidepressant with this combination of pharmacodynamic activities. In october, the committee for Medicinal Products for human use (chMP) under the European Medicines agency (EMa) adopted a positive opinion and recommended European marketing authorization of vortioxetine for MDD. The drug was made available in December, although a formal launch is planned for January 2014. In June 2013, sunovion Pharmaceuticals received FDa approval of lurasidone hydrochloride (latuda®) for two new indications: as monotherapy and as adjunctive therapy with either lithium or valproate, both to treat adult patients with major depressive episodes associated with bipolar I disorder. approval of the new indications was supported by two 6-week, double-blind, randomized, placebo-controlled trials, PREVaIl 2 (monotherapy) and PREVaIl 1 (adjunctive therapy; respective clinicalTrials. gov Identifiers NcT00868699 and NcT00868452). lurasidone is an atypical antipsychotic that has been marketed since 2011 for the treatment of schizophrenia. It was introduced for the new indication in late July. adasuve®, a new formulation of the typical antipsychotic loxapine succinate formulated using the staccato® inhalation system, was launched for the first time in 54 A.I. Graul et al. germany last July following approval by the European commission in February. In Europe, it is indicated for the rapid control of mild to moderate agitation in adult patients with schizophrenia or bipolar disorder. The marketing authorization requires that patients receive regular treatment immediately after control of acute agitation symptoms, and that the drug be administered only in a hospital setting under the supervision of a healthcare professional. adasuve was previously approved in the u.s. in 2012, as announced in last year’s edition of this article, but has not yet been launched in that country. alexza is responsible for manufacture and marketing of the product, which is distributed by Ferrer. loxapine succinate is a typical antipsychotic that was first launched in 1975 by Watson Pharmaceuticals in a capsule formulation for the treatment of psychosis. NEUROLOGIC DRUGS In the first quarter of 2013, Biogen Idec obtained FDa approval for dimethyl fumarate (Tecfidera™), indicated as a first-line treatment for people with relapsing forms of multiple sclerosis (Ms). Dimethyl fumarate is an orally administered immunomodulating and neuroprotective agent that provides a new approach to the treatment of Ms via activation of the Nrf2 pathway, although its exact mechanism of action is not fully understood. The Nrf2 pathway provides a way for cells in the body to defend themselves against inflammation and oxidative stress caused by conditions such as Ms (Fig. 2). Dimethyl fumarate has been clinically proven to significantly reduce important measures of disease activity, including relapses and development of brain lesions, as well as to slow disability progression over time, while demonstrating a favorable safety and tolerability profile. Biogen Idec launched the drug just days after approval. In september, the European commission approved the humanized anti-cD52 monoclonal antibody alemtuzumab (lemtrada™; genzyme) for the treatment of adult patients with relapsing–remitting Ms with active disease defined by clinical or imaging features. The approval was supported by the caRE-Ms I and caREMs II trials, in which alemtuzumab was significantly more effective than interferon β-1a at reducing annualized relapse rates. This is a new indication for alemtuzumab, which has been marketed by Bayer healthcare Pharmaceuticals since 2004 for the treatment of chronic lymphocytic leukemia. genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialization in Ms. ThoMsoN REuTERs – Drugs of Today 2014, 50(1) A.I. Graul et al. ThE YEaR’s NEW DRugs & BIologIcs 2013 Figure 2. Dimethyl fumarate is a second-generation fumarate derivative that is orally available and exhibits immunomodulatory properties. It has recently been shown to promote neuroprotection by upregulating antioxidative responses through the activation of nuclear factor, erythroid-derived 2, -like 2 (Nrf2), an effect that is believed to be independent of its immunomodulatory and radiosensitizing mechanisms. Its function as an Nrf2 activator is expected to have utility in treating relapsing-remitting multiple sclerosis. Istradefylline (Nouriast®), a first-in-class antiparkinsonian agent from Kyowa hakko Kirin, was approved for the first time worldwide last March in Japan. Istradefylline is a selective adenosine a2a receptor antagonist with a mechanism of action that is clearly distinct from that of other antiparkinsonians, most of which act on dopamine receptors (Fig. 3). adenosine a2a receptors are located in the basal ganglia, a region of the brain involved in motor control that is frequently degenerated or abnormal in Parkinson’s disease (PD). In clinical trials conducted in Japan, istradefylline improved wearing-off phenomena and was well tolerated in levodopa-treated PD patients. The drug is indicated for use in combination with levodopa-containing products, to treat wearing-off phenomena. It was launched in Japan in May. The tricyclic antidepressant clomipramine hydrochloride (anafranil®), which has been marketed since the ThoMsoN REuTERs – Drugs of Today 2014, 50(1) 1960s for the treatment of anxiety and depression, was approved and launched last year for the first time in Japan for a new indication: treatment of cataplexy in patients with narcolepsy. This is the first time that a regulatory body has officially approved clomipramine for this use, although it has long been prescribed off-label for patients with cataplexy, and in fact alfresa filed the application for this indication based on evidence in the public domain. Japan has the world’s highest prevalence of narcolepsy: 1 in 600 inhabitants, according to the Narcolepsy Network. RESPIRATORY DRUGS Breo™ Ellipta™ (glaxosmithKline[gsK]/Theravance), a fixed-dose combination product incorporating the inhaled corticosteroid fluticasone propionate and vilanterol, a long-acting β2-adrenoceptor agonist (laBa), was approved last year for the first time in the 55 an alternative approach is the implementation of nondopaminergic therapy. once-daily maintenance treatment of airflow obstruction in patients with coPD. ultibro is a first-in-class combination product containing the laBa indacaterol and the long-acting muscarinic antagonist (laMa) glycopyrronium bromide. In November. including chronic bronchitis and/or emphysema.406 patients and 11 clinical studies in 7.u. which entails the modulation of adenosine receptors. a2a receptor activation blocks D2 receptor signaling. for a different respiratory indication: the treat56 ment of bronchial asthma in adults and adolescents aged 12 years and older in cases where concurrent use of an inhaled corticosteroid and a long-acting β2-adrenoceptor agonist is required. The loss of dopamine input into the neostriatum is a key characteristic of Parkinson’s disease (PD). for both indications: asthma and coPD. where it is known as Relvar™ Ellipta™. It is indicated in the u. as an inhaled long-term.s. and is formulated as inhalation capsules for use with the Breezhaler® device. It is also indicated to reduce exacerbations of coPD in patients with a history of exacerbations. facilitates responses to dopamine and neurotransmitters of motor function/cognition. in october 2013. 50(1) . Relvar Ellipta was approved in the E.s.ThE YEaR’s NEW DRugs & BIologIcs 2013 A..I. There were four primary coPD studies: two 6-month lung function studies and two 1-year replicate exacerbation studies. adenosine a2a receptors are heavily populated within the striatum and directly associated with dopamine D2 receptors. their extended use may result in diminished efficacy and debilitating dyskinesia. The same combination product was also approved last year in Japan. The suppression of a2a receptor activity by antagonists such as istradefylline is therefore expected to heighten dopamine-mediated responses in PD. Data supporting the approval included findings from a program of nonclinical studies. Dual bronchodilation with ultibro is ThoMsoN REuTERs – Drugs of Today 2014. with which they share a reciprocal function. a neuromodulator.851 patients with coPD. 52 clinical pharmacology studies in 1. another new combination product for coPD —ultibro® (glycopyrronium bromide/indacaterol)— was also approved last september in both the European union and Japan. u. for the treatment of chronic obstructive pulmonary disease (coPD). i.s. The product was developed using a dry powder formulation technology for inhalation products licensed by gsK from skyePharma.e. Figure 3. adenosine. although dopamine replacement therapy using dopamine precursors assuages motor symptoms. its first coPD market. Graul et al. Breo Ellipta was launched in the u. canada. In october 2013. followed later in the year by the u. The first product launches took place in germany and the Netherlands.s. Iceland and the u. The first country in which launch took place was the u. and was developed to simplify treatment regimens. shionogi’s Irtra®. The combination of a renin-angiotensin blocker and a low-dose diuretic is recommended in Japanese guidelines for hypertension therapy. engineered version of natural human lung surfactant. and Japan. containing irbesartan and atorvastatin calcium.K. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 for the first time in Japan. Robelito is indicated to reduce the risk of heart disease in patients with hypertension and hyperlipidemia who are already prescribed the two active drugs. partners Bristol-Myers squibb and Pfizer began rolling out the coagulation factor Xa inhibitor apixaban (Eliquis®) in markets worldwide for a new indication: the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The endothelin ETa/ETB antagonist macitentan (opsumit®. a widely marketed statin. due to their synergistic antihypertensive activity and favorable side effect profile.s. The efficacy of macitentan was established in the pivotal study sERaPhIN (clinicalTrials. 4). Prior to the introduction of riociguat. Bayer) was approved and launched in canada. apixaban was first launched in 2011 for the prevention of venous thromboembolic events in adults who have undergone elective hip or knee replacement surgery. It is the first FDa-approved synthetic. according to product codevelopers Novartis and sosei. It was codeveloped by Toa Eiyao and Nitto Denko. Denmark. a new fixed-dose combination product from astellas incorporating the α1-adrenoceptor antagonist 57 . in a single tablet. cTEPh affects up to several thousand patients in canada.s. Who group I). a humanized. a new long-acting β2-adrenoceptor agonist from Boehringer Ingelheim. resulting in an overload of the right heart. was launched for the first time in the u. there were no proven pharmacotherapeutic alternatives for patients with inoperable or persistent cTEPh. also in 2013. Bisono Tape is the first transdermal patch formulation of a β-blocker to reach the market anywhere in the world. Irtra contains the angiotensin aT1 receptor antagonist irbesartan and trichlormethiazide. Olodaterol hydrochloride (striverdi® Respimat®). for the treatment of adults with pulmonary arterial hypertension (Pah. becoming the first drug ever to obtain regulatory approval for this rare disease (Fig. was approved last year in several countries including Russia. actelion) was approved and launched last year for the first time in the u. another irbesartan-containing fixed-dose combination reached its first market last year in Korea: hanmi and sanofi’s Robelito. a new treatment option became available to Japanese patients with mild to moderate essential hypertension: Bisono® Tape. expected to set a new standard of care in coPD. and is marketed and distributed by astellas. a fixed-dose combination antihypertensive agent. a randomized. chronic thromboembolic pulmonary hypertension (cTEPh) is a progressive and life-threatening type of pulmonary hypertension in which thromboembolic occlusion of pulmonary vessels gradually leads to increased blood pressure in the pulmonary arteries. 5. Lucinactant (surfaxin®.3 million patients are currently living with coPD in Japan.s.I. The laBa was developed as a fast-acting and longlasting bronchodilator for once-daily maintenance treatment of airflow obstruction in patients with coPD. in November 2013. in January 2013. a diuretic. CARDIOVASCULAR DRUGS over the course of 2013. In addition. last year the first-in-class soluble guanylate cyclase stimulator riociguat (adempas®. lucinactant is indicated for the prevention of respiratory distress syndrome (RDs) in premature infants at high risk for RDs. the EMa’s committee for Medicinal Products for human use issued a positive opinion on the use of macitentan in Pah. a once-daily transdermal patch formulation of the established β1-adrenoceptor antagonist bisoprolol.gov Identifier NcT00660179).A. coPD is a progressive disease affecting up to 10% of adults across Europe and is projected to be the third leading cause of death by 2020. peptide-containing surfactant and the only alternative to animal-derived surfactants available in the u. RENAL–UROLOGIC DRUGS Vesomni™. Graul et al. including chronic bronchitis and emphysema. was also approved and launched last year ThoMsoN REuTERs – Drugs of Today 2014. controlled trial involving 742 patients with Pah with predominantly Who functional class II-III symptoms treated for an average of 2 years. to delay disease progression. with launch in Japan following shortly thereafter. Discovery laboratories). The product carries a boxed warning alerting patients and healthcare professionals that it should not be used in pregnant women because it can harm the developing fetus.K. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. control and satisfaction in two pivotal. Increased cgMP levels result in the inhibition of calcium channels and decreased intracellular calcium release. was approved for the first time in May in the Netherlands and was launched there in september. Graul et al.000 exposures. an antimuscarinic.I. placebo-controlled. Plethora solutions holdings received marketing authorization from the European commission for Prilocaine Lidocaine Plethora (PsD-502). Filing with the FDa is anticipated for early 2014. Men with the disorder ThoMsoN REuTERs – Drugs of Today 2014. Figure 4. involved in muscle cell relaxation and vasodilatation. indicated for the treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy. placebo-controlled phase III IMPREss I and II studies in subjects with Peyronie’s disease.s. phase III studies. leads to blood vessel dilation. In December 2013. Thus. Vesomni is indicated for the treatment of moderate to severe storage symptoms (urgency. The safety and efficacy of Xiaflex were evaluated in the randomized. In November. the compound promotes the catalyzing of cyclic guanosine monophosphate (cgMP). The Netherlands will act as Reference Member state for further registration of the product throughout Europe. tamsulosin hydrochloride and solifenacin succinate. By stimulating sgc. the diminution of blood pressure and the modulation of tissue-protective effects. It was also well accepted by subjects in over 23. auxilium). a topical spray incorporating two local anesthetics. The treatment was associated with significant improvement 58 in the primary measures of intravaginal ejaculation latency time. Riociguat (also known as BaY-63-2521) is an oral soluble guanylate cyclase (sgc) activator that is expected to be useful for treating pulmonary arterial hypertension (Pah). activation of cgMP-mediated protein kinase and myosin light chain protein. increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia in men who are not adequately responding to treatment with monotherapy. the u. 50(1) . and the first European launch is expected later in the year. FDa approved the first pharmacotherapeutic agent ever for the treatment of Peyronie’s disease: collagenase Clostridium histolyticum (Xiaflex®. double-blind. double-blind. indicated for the treatment of primary premature ejaculation. gc activators may be effective in the treatment of Pah and associated disorders such as chronic thromboembolic pulmonary hypertension. auxilium immediately began commercializing the product for this new indication. HEMATOLOGIC AGENTS The FDa approved Baxter’s Rixubis (nonacog gamma.8 ± 3. phosphorus binds to calcium to form calcium phosphate. was approved by the European commission in February and launched in its first markets —germany and austria— in april.gov Identifier NcT01174446).s. actively transports glucose by coupling with Na+. Turoctocog alfa (NovoEight®).s.2% improvement in those randomized to placebo. The inhibition of renal sglTs leads to suppression of tubular glucose reabsorption and the excretion of excess plasma glucose into urine. a non-absorbed anion exchange resin and phosphate binder. which can lead to hyperphosphatemia. awaiting the expiration of existing patents.5. Because this represents an increased risk for cardiovascular disease. switzerland and singapore. were randomized to receive a maximum of four treatment cycles at 6-week intervals of Xiaflex or placebo administered by intralesional injection. ENDOCRINE DRUGS The sodium/glucose cotransporter (sglT). This goal became easier last year with the approval of two new products developed specifically for this purpose.3/day) as compared to sevelamer carbonate.I.8 vs. The approval was based on a phase I/III study demonstrating that twice-weekly prophylactic treatment with Rixubis for 6 months achieved a median annualized bleed rate of 2. where decisions are expected in the first half of 2014. It is indicated for the control and prevention of bleeding. The iron-based phosphate binder sucroferric oxyhydroxide (Velphoro®. which has been marketed in Japan (as cholebine®) since 1999 for the treatment of hypercholesterolemia. was approved last year by the u. although sglT2 inhibitors in particular are held to be especially promising for the treatment of type 2 diabetes.8 ± 3. The product is also under regulatory ThoMsoN REuTERs – Drugs of Today 2014. additionally. In patients with reduced renal function. FDa for use in adults and children with hemophilia a. In persons with diabetes and/or obesity. as this action can reduce hyperglycemia and glucoserelated osmotic dehydration of cells. Xiaflex was previously approved by the FDa in 2010 for the treatment of Dupuytren’s contracture.0 with 43% of patients experiencing no bleeds (clinicalTrials. The first sglT2 inhibitor. coagulation factor IX [recombinant]) in June. indicated for routine prophylactic treatment. glucose and energy loss through excretion is advantageous. control of bleeding episodes and perioperative management in adults with hemophilia B. Velphoro will be launched in the u. phosphorus is not sufficiently excreted into the urine via the kidneys and accumulates in the body. Rixubis is the first new recombinant coagulation factor IX (rFIX) approved for hemophilia B in more than 15 years and is the only rFIX indicated for both routine prophylaxis and control of bleeding episodes in the u. the current standard of care. which in turn causes calcinosis on vascular walls. thereby eliminating hyperglycemia. lungs and other internal organs. This is a new indication for colestilan. as compared to 18. Baxter launched the product in the u. respectively). Novo Nordisk plans to launch turoctocog alfa in the u. Persistent hyperphosphatemia causes secondary hyperparathyroidism and even nephrogenic osteopathy characterized by bone pain and a tendency for bone fracture. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 review in Europe. heart. colestilan is indicated for the treatment of hyperphosphatemia in adult patients with chronic kidney disease (cKD) stage 5 receiving hemodialysis or peritoneal dialysis. Graul et al. Both low-affinity (sglT2) and high-affinity (sglT1) forms have been studied for this indication. symptom bother scores also improved to a significantly greater extent with Xiaflex as compared to placebo (–2. and shortly thereafter filed for marketing approval in the European union. perioperative management. The study demonstrated that Velphoro successfully controls hyperphosphatemia with fewer pills (average of 3. and Puerto Rico in october. Vifor Pharma) was approved by the FDa in November 2013 for the control of serum phosphorus levels in patients with cKD on dialysis. Men randomized to the active treatment showed a mean 34% improvement in penile curvature. –1. and routine prophylaxis to prevent or reduce the frequency of bleeding episodes.s. by Fresenius in 2014. the management of serum phosphate levels in patients with renal disease is of paramount importance. The approval was based on a pivotal phase III study which met both its primary and secondary endpoints. for adult patients living with this chronic condition. a recombinant coagulation factor VIII product from Novo Nordisk.s.A. Mitsubishi Tanabe Pharma’s colestilan (BindRen®).s. as well as periarticular areas. last year the product also received a positive opinion from the European Medicines agency’s committee for Medicinal Products for human use. shortly after april 2015. 59 . which exists on the chorionic membrane of the intestine and the kidney. canagliflozin is the first sglT2 inhibitor to achieve marketing approval in the u. Graul et al.s. while offering less risk of hypoglycemia —especially at night— compared with insulin glargine. shionogi obtained exclusive global marketing rights to the sERM under a license agreement signed with QuatRx Pharmaceuticals in 2010. Its safety and effectiveness were established in 3 clinical studies of 1.45 per thousand women. as the first nonhormonal therapy for vasomotor symptoms (VMs) associated with menopause. ThoMsoN REuTERs – Drugs of Today 2014. These rates are considered to represent low risks in contrast to the increased risks of stroke and deep vein thrombosis seen with estrogen-alone therapy. with a favorable safety profile.889 postmenopausal women with symptoms of VVa. The product is indicated for use as monotherapy and as part of a combination therapy for the treatment of type 1 and type 2 diabetes in adults. Kazano is indicated as an adjunct to diet and exercise. osphena carries a boxed warning alerting women and healthcare professionals that the drug. results from the first two trials showed a statistically significant improvement of dyspareunia in ospemifene-treated women compared with those receiving placebo. The novel insulin analogue insulin degludec (Tresiba®).72 and 1. 50(1) . ospemifene (osphena®. do not provide adequate glycemic control. can stimulate the lining of the uterus and cause it to thicken.500 patients with type 2 diabetes.K. however. was launched in Europe in 2012 and last year the second compound in this important new class of diabetic drugs reached the market: Janssen’s Invokana™ (canagliflozin) was approved by the FDa in March for the treatment of adults with type 2 diabetes. shionogi). Many women are unable or unwilling to take hormone therapy to treat VMs.45 per thousand women). Paroxetine mesilate has been marketed since 2001 for the treatment of depression. a novel fixed-dose combination therapy incorporating the dipeptidyl peptidase 4 (DPP IV) inhibitor alogliptin benzoate and metformin hydrochloride. which acts like estrogen on vaginal tissues. a biguanide insulin sensitizer. a new low-dose formulation of the selective serotonin reuptake inhibitor (ssRI) paroxetine mesilate.ThE YEaR’s NEW DRugs & BIologIcs 2013 dapagliflozin. (sERM) that was approved and launched in the u. was launched for the first time last year in the u. respectively) and the incidence rate of deep vein thrombosis (1. Results from the third study support the product’s long-term safety in treating dyspareunia.. It was launched in the u. In phase II and III studies enrolling a total of 1. Women should see their healthcare professional if they experience any unusual bleeding as it may be a sign of endometrial cancer or a condition that can lead to it.I.. the glP-1 receptor agonist lixisenatide (lyxumia®). lixisenatide was developed by sanofi under license from Zealand Pharma. The product was developed by Noven Pharmaceuticals to treat hot flashes and night sweats associated with menopause. after 12 weeks of treatment. together with diet and exercise. a new incretin mimetic. Takeda’s Kazano®. is a selective estrogen receptor modulator 60 A. It has also been approved in Mexico. More than half of u.s. Two new products reached the market last year and a third was approved that will help to ease the transition through menopause for the growing global population of aging women. although the vast majority of them do not receive treatment.u.s.s. women will experience VVa at some point during their postmenopausal life. Brisdelle™. Novo Nordisk supplies insulin degludec in its FlexTouch® prefilled disposable pen. often leaving symptoms untreated. as well as Norway. was approved and launched last year in the u. to improve glycemic control in adults with type 2 diabetes mellitus. The first. was approved by the European commission in February 2013 for use in the 27 member countries of the E. It is indicated for the treatment of adults with type 2 diabetes in order to achieve glycemic control in combination with oral glucose-lowering medicinal products and/or basal insulin when these. due to menopause. where it has been available since april 2013. treatment with paroxetine mesilate for 24 weeks led to reductions in the frequency and severity of moderate to severe hot flashes.276 women with VMs associated with menopause. was launched last March for the first time in Denmark and just a few days later in Japan. The boxed warning also states the incidence rates of thrombotic and hemorrhagic strokes (0. The safety and efficacy of the product were demonstrated in 4 clinical trials involving more than 2. ospemifene is the first and only oral alternative to vaginal or oral steroidal estrogens for women with dyspareunia due to menopause. The new long-acting insulin is designed for once-daily dosing and has been shown to lower blood glucose levels. for the treatment of moderate to severe dyspareunia. Iceland and liechtenstein. a symptom of vulvar and vaginal atrophy (VVa). its first market. ospemifene should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.s. a once-daily basal insulin from Novo Nordisk. later in the first quarter. The product was discovered by Zeria and was licensed exclusively to astellas for codevelopment and marketing. decreases the synthesis of proinflammatory cytokines and may reduce T-cell infiltration at sites of inflammation. DERMATOLOGIC DRUGS In august 2013. itolizumab was approved by the Drugs controller general of India for the treatment of moderate to severe chronic plaque psoriasis. golimumab is a human monoclonal antibody that targets and neutralizes excess TNF-α. It is believed to improve hIV-associated diarrhea via a dual mechanism of action. with a history of diarrhea for 1 month or more (clinicalTrials. By blocking achE and inhibiting the degradation of acetylcholine. azathioprine or 6-mercaptopurine. and thus improves symptoms of functional dyspepsia such as postprandial fullness. It is also approved for use with methotrexate for the treatment of moderately to severely active rheumatoid arthritis. Biocon launched alzumab™ (itolizumab). applied once daily. and was subject to a joint research. In addition. The u. adhesion and maturation of T cells. upper abdominal bloating and early satiation. i. the FDa approved galderma’s Mirvaso® (brimonidine tartrate). an α2-adrenoceptor agonist and vasoconstrictor. By binding to cD6. a peripheral acetylcholinesterase (achE) inhibitor. placebo-controlled (1-month) and placebo-free (5-month). galderma launched Mirvaso in september. and active ankylosing spondylitis. The primary efficacy endpoint was the proportion of patients experiencing two watery bowel movements or less per week during at least 2 of the 4 weeks of the placebo-controlled phase of the study. Duavee is the first FDa-approved medication that contains an estrogen in combination with a sERM. but until now there were no approved drugs to treat it. Pfizer plans to introduce Duavee in February 2014. has been marketed for many years as an ocular formulation for the treatment of glaucoma and ocular hypertension. bazedoxifene. the drug is also indicated to induce clinical remission and achieve and sustain clinical remission in induction responders. acotiamide improves impaired gastrointestinal motility and delayed gastric emptying. The sERM component reduces the risk of endometrial hyperplasia that can occur with the estrogen component. the first topical treatment specifically developed and indicated for the treatment of facial erythema of rosacea. discovery and development agreement signed with ligand in september 1994. FDa approval was based on a randomized. was approved and launched last year for the first time in Japan. resulting in reduced chloride ion secretion into the gastrointestinal lumen. Data demonstrated that a significantly larger pro61 .e. where it is indicated for the treatment of functional dyspepsia. inhibition of both the cystic fibrosis transmembrane conductance regulator (cFTR) and the calcium-activated chloride channel (cacc). cD6 is a pan T-cell marker involved in costimulation. Janssen Biotech’s golimumab (simponi®) was approved and launched last year in the united states for a new indication: the treatment of moderately to severely active ulcerative colitis in adults who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates.I. multicenter study in 374 hIV-positive patients on aRT.. was the site of the first launch last year of Fulyzaq™ (crofelemer) delayed-release tablets. Based on the results of a 52-week phase III trial conducted in India. in India. Duavee was originally developed at Wyeth (now Pfizer). which play a leading role in autoimmune disease (Fig. also in august.s. a first-in-class humanized monoclonal antibody directed against the T-cell differentiation antigen cD6. Pfizer’s fixed-dose combination product Duavee™ (conjugated estrogens/bazedoxifene) was approved in the u. oral corticosteroids. Brimonidine. Mirvaso works quickly to reduce the redness of rosacea and lasts for up to 12 hours. itolizumab downregulates T-cell activation. Patients who received concomitant antidiarrheal medications or opiates were counted as clinical nonresponders. GASTROINTESTINAL AGENTS The gastroprokinetic agent acotiamide hydrochloride hydrate (acofide®).s. crofelemer is derived on a sustainable basis from the Croton lechleri plant.A. acotiamide is the first agent approved for use in patients with functional dyspepsia diagnosed according to Rome III diagnostic criteria. in women with a uterus. Graul et al. It is indicated. acetylcholine is an ThoMsoN REuTERs – Drugs of Today 2014. In october. Erythema (redness) is a common symptom of rosacea. active psoriatic arthritis alone or with methotrexate. approved by the FDa for the symptomatic relief of noninfectious diarrhea in patients with hIV/aIDs on antiretroviral therapy (aRT). 5). double-blind. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 important neurotransmitter for regulating gastrointestinal motility.gov Identifier NcT00547898). for the treatment of moderate to severe vasomotor symptoms associated with menopause and for the prevention of postmenopausal osteoporosis. osteopenia and weight loss due to the reduced intestinal capacity to absorb nutrients. Teduglutide has orphan drug status for the indication of sBs. severe diarrhea. as a treatment for adult patients with short bowel syndrome (sBs). Itolizumab is a humanized Igg1 immunosuppressive monoclonal antibody that selectively inhibits the cell surface receptor cD6 and is predicted to be useful in the therapeutic intervention of chronic plaque psoriasis. The antibody binds to cD6. crofelemer did not influence the efficacy or safety of the patients’ hIV medications. dehydration. portion of patients taking crofelemer 125 mg twice daily experienced a clinical response compared with patients in the placebo group.I. Furthermore. which in turn binds to its ligand cD166. Teduglutide is a recombinant analogue of human glucagon-like peptide 2 (glP-2). the crofelemer treatment effect for clinical response (125 mg twice daily vs. statistically significant reductions from baseline to the end of the double-blind period were also observed for the number of watery bowel movements per day and daily stool consistency score among patients taking crofelemer compared with placebo. In addition. resulting in the suppression of T-cell activation and reduced proinflammatory cytokine production. a prescription medical food product. The drug is distributed in the u. by salix Pharmaceuticals under license from Napo Pharmaceuticals. Graul et al. bronchitis. placebo) was similar in subgroup analyses based on duration of diarrhea. The most common adverse reactions in the study were respiratory tract infection. baseline number of daily watery bowel movements. last summer. 50(1) . ischemia or other conditions. It may additionally offset T-cell infiltration at sites of inflammation. This highly disabling condition typically develops following surgical resection of the bowel due to crohn’s disease. Figure 5. and can lead to serious life-threatening complications. Patients with sBs often suffer from malnutrition. a naturally occurring protein involved in the rehabilitation of the intestinal lining.s.s. water and electrolytes. ThoMsoN REuTERs – Drugs of Today 2014. flatulence and increased bilirubin. 62 NPs Pharmaceuticals’ teduglutide [rDNA origin] (gattex®) was launched for the first time last year in the u. cough.ThE YEaR’s NEW DRugs & BIologIcs 2013 A. use of protease inhibitors and cD4 cell count. Entera health launched its oral serumderived bovine immunoglobulin protein isolate EnteraGam™. fatigue. simeprevir works by blocking the protease enzyme that enables the hepatitis c virus (hcV) to replicate in host cells. The company is currently working on resubmitting the application to the FDa. ANTI-INFECTIVE THERAPY In august the FDa approved ViiV healthcare’s Tivicay® (dolutegravir) for use in combination with other antiretroviral agents for the treatment of hIV-1 in adults and children aged 12 years and older. This approval allows for the marketing of Tybost in all 28 countries of the European union. and canada. abacavir and lamivudine. and E.s. gilead received marketing authorization from the European commission for oncedaily cobicistat (Tybost®). Finally. The sPRINg-2 trial compared a oncedaily dolutegravir-based regimen to twice-daily raltegravir. another hIV integrase inhibitor. was approved in the E. for the treatment of genotype 1 chronic hepatitis c in adult patients with compensated liver disease. like elvitegravir. it was not approved as a single agent until 2013.u. as well as manage immune function and mucosal barrier function in the intestine. weighing at least 40 kg. while sINglE evaluated once-daily dolutegravir and abacavir/lamivudine compared to once-daily atripla® (efavirenz/emtricitabine/tenofovir disoproxil fumarate). administered once daily with pegylated interferon and ribavirin.gov Identifier NcT01328041). Elvitegravir is also a component of gilead’s stribild™ (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg).u. It is indicated for the treatment of hIV-1 infection in adults ThoMsoN REuTERs – Drugs of Today 2014. another trial. absorb or metabolize ordinary foodstuffs or certain nutrients. digest.s. cobicistat was approved in 2012 as a component of the combination product stribild. gilead is currently working with regulatory authorities throughout the European union to bring Vitekta to patients as quickly as possible.. or who have chronic loose or frequent stools (e.s. it was approved in both the u. as part of hIV treatment regimens that include a ritonavir-boosted protease inhibitor. The approval was supported by data from 4 pivotal phase III trials enrolling 2. elvitegravir was effective in suppressing hIV among patients with drug-resistant strains of hIV. The following month. clinicalTrials. have limited or impaired capacity to ingest.s. Enteragam. In November. diarrhea-predominant irritable bowel syndrome [IBs-D]). In october. Tybost is indicated as a boosting agent for the hIV protease inhibitors atazanavir 300 mg once daily and darunavir 800 mg once daily as part of antiretroviral combination therapy in adults with hIV-1 infection. the FDa’s antiviral Drugs advisory committee voted 19 to 0 to recommend approval of simeprevir. the fourth trial. assessed the effectiveness of twice-daily dolutegravir on viral load in treatment-experienced patients with resistance to multiple classes of hIV medicines. including cirrhosis. 63 . and in patients with chronic loose or frequent stools who are infected with hIV. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 without known mutations associated with resistance to elvitegravir. including resistance to integrase inhibitors. gilead’s elvitegravir (Vitekta™). 2 of which (sPRINg-2 and sINglE. Simeprevir is an Ns3/4a protease inhibitor jointly developed by Janssen and Medivir for the treatment of genotype 1 and 4 chronic hepatitis c in adult patients with compensated liver disease. last september it was approved for the first time in Japan. a cytochrome P450 3a4 inhibitor and pharmacokinetic enhancer that increases blood levels of certain hIV medicines. a serum-derived bovine immunoglobulin/protein isolate (sBI). in November. however. including all stages of liver fibrosis. During the third quarter. ViiV filed marketing applications in the u. gilead submitted an NDa to the FDa for cobicistat as a single agent in June 2012 and received a complete Response letter in april 2013.gov Identifier NcT01263015) compared a once-daily dolutegravir-based regimen to twice-daily raltegravir in treatment-experienced patients who had not previously been treated with an integrase inhibitor.A.557 adults with hIV. Dolutegravir was launched in the u. Enteragam is indicated for the clinical dietary management of enteropathy under medical supervision for patients who.. because of therapeutic or chronic medical needs.g. Graul et al. In clinical trials. has been shown in clinical studies in diverse disorders to improve gastrointestinal nutrient absorption. which was called VIKINg-3 (clinicalTrials. shortly after approval. In the u. called saIlINg (clinicalTrials.gov Identifiers NcT01227824 and NcT01231516) included treatmentnaive patients.I. a once-daily single tablet regimen for hIV that was approved in the united states in august 2012 for treatment-naive adults and by the European commission in May 2013 for adults who are treatmentnaive or who have no known mutations associated with resistance to any of the three antiretroviral agents contained in the combination product. for a single-tablet formulation incorporating dolutegravir. Dolutegravir is an integrase inhibitor that blocks hIV replication by preventing the viral DNa from integrating into the genetic material of human immune cells. in april 2013. gilead).s. which has FDa Breakthrough Therapy Designation. Graul et al. In December 2013. but should not be used as monotherapy. 6). Janssen launched bedaquiline in the u.s. The product. indicated for the treatment of hcV infection as a component of a combination antiviral treatment regimen. sofosbuvir. FDa granted accelerated approval to Janssen Therapeutics for bedaquiline (sirturo™).. Thus the development of several new classes of antituberculosis drugs has been regarded with great interest and has begun to bear fruit. 7). 50(1) . in December. a virus-specific biochemical activity that has not been observed in mammalian cells (Fig. the RNa-dependent RNa polymerase encoded by Ns5B. the first new TB drug in 40 years. 2. particularly due to the emergence in recent years of multidrug-resistant (MDR) strains. acts as an RNa-directed RNa polymerase (Ns5B) inhibitor and is expected to be useful for treating chronic hepatitis c virus (hcV) infection. is essential for hcV replication. Bedaquiline. the enzyme required by Mycobacterium tuberculosis to replicate and spread through the body (Fig. In the last days of 2012. The drug has demonstrated efficacy in subjects with hcV genotype 1. was launched in the u. The interim guidance was developed using lim- Figure 6. which bind to one of several allosteric binding sites on the hcV polymerase. to treat adults (18 years or older) with MDR-TB when other alternatives are not available. is the first targeted inhibitor of proton-translocating aTP synthetase (F0F1 aTPase). Tuberculosis (TB) is a major public health concern around the world. sofosbuvir can be used in combination with ribavirin or peginterferon alfa/ribavirin. the World health organization (Who) issued interim policy guidance on the use of bedaquiline in the treatment of MDR-TB.I. The Ns5B enzyme is targeted by both nucleoside inhibitors.ThE YEaR’s NEW DRugs & BIologIcs 2013 and in December the product was launched in its first markets: Japan (as sovriad®) and the u. as well as those with hcV/hIV-1 co-infection. a chirally pure isomeric form of PsI-7851. hepatitis replicase. the u. the u. 3 or 4 infection and hepatocellular carcinoma (awaiting liver transplantation). and by nonnucleoside inhibitors. In June. which bind to the active catalytic site. FDa approved sofosbuvir (sovaldi™. its first market. It functions by suppressing the RNa polymerase that hcV utilizes to facilitate the replication of its RNa.s. indicated as part of combination therapy. (as olysio™). This enzyme synthesizes viral RNa using an RNa template.s.s. A. a first-in-class nucleoside analogue Ns5B inhibitor. 64 ThoMsoN REuTERs – Drugs of Today 2014. The Who strongly recommended the acceleration of phase III trials to generate a more comprehensive evidence base to inform future policy on bedaquiline. anthracis that can cause massive and irreversible tissue injury and death (Fig. The guideline thus lists five conditions that must be in place if bedaquiline is used in combination therapy to treat adults with MDR-TB: effective treatment and monitoring. 50(1) 65 . Raxibacumab is the first monoclonal antibody approved under the FDa’s animal Efficacy Rule.s. Bedaquiline is thus expected to be a potent treatment option for tuberculosis. Graul et al. Bedaquiline (also designated TMc-207) is a diarylquinoline that acts as a mycobacterial F0-F1 aTP synthase inhibitor and is reported to be effective against both drug-susceptible and multidrug-resistant strains of Mycobacterium tuberculosis.A. indicated for the treatment of adult and pediatric patients with inhalational ThE YEaR’s NEW DRugs & BIologIcs 2013 anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs and for the prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. the FDa’s accelerated approval of the drug was based on two phase IIb trials. In this case. it was not possible to conduct adequate efficacy trials in humans. FDa approved the first anthrax antitoxin. The safety of raxibacumab was evaluated in 326 healthy human volunteers. In December 2012. hgs was acquired by gsK in august 2012. informed consent.s.I. because inhalational anthrax is a rare and lethal disease. The organization will review. ited evidence available from clinical trials. proper patient inclusion (caution is required when bedaquiline is used in people aged 65 and over and in adults with hIV). raxibacumab. adherence to Who recommendations on MDR-TB treatment regimens. and active pharmacovigilance and management of adverse events. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. Department of health and human services’ Biomedical advanced Research and Development authority. Inhibition of the enzyme is expected to result in the depletion of aTP. and the agent’s effectiveness was therefore demonstrated in one study in monkeys and three studies in rabbits. ThoMsoN REuTERs – Drugs of Today 2014. Raxibacumab was developed by human genome sciences (hgs) in conjunction with the u. revise or update the interim guidance as additional information on efficacy and safety becomes available. 8). and gsK began mar- Figure 7. The enzyme aTP synthase is essential for aTP synthesis and energy metabolism. the u. which consequently diminishes the chances of pathogen survival. In study 1. for the treatment of adult patients with frequent gouty arthritis attacks in whom NsaIDs and colchicine are con- Figure 8.5% of subjects treated with vehicle.8% of subjects treated with efinaconazole were completely cured.s. including subjects in canada. Raxibacumab is a human monoclonal antibody that is directed against the Bacillus anthracis protective antigen component (Pac) and is thus predicted to have utility in the therapeutic intervention of anthrax infection. including the potential for acute liver injury. where it is indicated for the treatment of mild to moderate onychomycosis. In March it was approved in the E. 15. thereby blocking the fatal entry of anthrax toxins into cells. marketed since 2009 for the treatment of cryopyrin-associated periodic syndromes. 17. In september. In study 2. was approved and launched last year for two new indications. under which gsK will provide 60.000 doses to the national stockpile over a period of 4 years.I.u. In several animal models. 50(1) . which required that the target nail show no A. Graul et al. the drug has demonstrated effectiveness in protecting against death induced by anthrax spore inhalation. Novartis). oral treatments are limited by drug interactions and numerous safety concerns. Pivotal international studies of efinaconazole were conducted in 1. clinical involvement and no evidence of fungus present by both Koh testing and a negative fungal culture. 66 ThoMsoN REuTERs – Drugs of Today 2014. THERAPY OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES The anti-interleukin-1β (Il-1β) human monoclonal antibody canakinumab (Ilaris®. This common and destructive fungal nail infection is unusually difficult to treat. Valeant has not yet set a launch date for the product. government.s. For the pivotal studies. last year the triazole antifungal agent efinaconazole (Jublia®.2% of subjects treated with efinaconazole were completely cured. government in 2013.3% of subjects treated with vehicle. gsK announced a new contract with the u. compared to only 3. compared to only 5. The antibody acts by preventing the Pac from binding to cell surfaces. Valeant) was approved for the first time in canada.ThE YEaR’s NEW DRugs & BIologIcs 2013 keting the monoclonal antibody to the u.655 subjects with onychomycosis. laser treatments only improve the appearance of the nail. the primary endpoint was complete cure at week 52. 51% (24/47) had a duration of response of at least 8 months. a monoclonal antibody that binds to TNF ligand superfamily member 11 (RaNKl). This was the first approval allowing the use of the product in children. The most common adverse reactions were arthralgia. safety data was evaluated in 304 patients with gcTB who received at least 1 dose of denosumab. The safety profile of denosumab in patients with gcTB was similar to that reported in studies of patients with bone metastases. In 2013. was based on encouraging results from 2 open-label trials that enrolled a total of 305 patients with gcTB that was either recurrent. following a priority review. multicenter. canakinumab became available for u. resulting in pain. but is not limited to.s. cimzia has been available since 2008 for the treatment of crohn’s disease and since 2009 for rheumatoid arthritis. patients with sJIa during the second quarter. Three patients experienced disease progression following an objective response. fatigue and pain in the extremity. Bivigam is a sugar-free. Denosumab has been available for several years for the treatment of skeletal-related events in patients with bone metastases from solid tumors. an ongoing. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. the company also obtained FDa approval for another new indication for certolizumab pegol: the treatment of adults with active ankylosing spondylitis. the most severe form of cryopyrin-associated periodic syndromes (caPs). anakinra is a recombinant form of the Il-1 receptor antagonist protein that blocks the biological activity of Il-1 by binding to Il1 receptor type 1. for the psoriatic arthritis indication. or do not provide adequate response. glycine stabilized intravenous immune globulin approved by the FDa for use in patients with primary humoral immunodeficiency. amgen began marketing it for the new indication immediately upon receipt of approval. Biotest Pharmaceuticals announced the u. and also appeared to be similar in skeletally mature adolescents and adults.I. In addition to these three new indications. or for which planned surgery was likely to result in severe morbidity. nausea. headache.s. approval of denosumab. Kineret was approved under an orphan drug designation and an FDa priority review.A. launch of Bivigam™ (immune globulin intravenous [human]) 10% liquid. This includes. the FDa approved ucB’s cimzia® (certolizumab pegol) for the treatment of adult patients with active psoriatic arthritis. anakinra was discovered and developed by amgen. The estimated median time to response was 3 months. who have had an inadequate response to or are intolerant to NsaIDs. It was rolled out for this indication in germany and greece later in the year. of these patients. the European commission approved the product for the treatment of adult patients with severe active axial spondyloarthritis. the FDa approved a new indication for denosumab (amgen’s Xgeva®) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (gcTB) that is unresectable or where surgical resection is likely to result in severe morbidity.gov Identifier NcT01087788). sobi began marketing anakinra for the new indication during the second quarter of 2013. The overall ThoMsoN REuTERs – Drugs of Today 2014. for the treatment of active systemic juvenile idiopathic arthritis (sJIa) in patients aged 2 years and older. back pain. In october. placebocontrolled phase III trial designed to evaluate the efficacy and safety of certolizumab pegol in 409 patients with active and progressive adult-onset psoriatic arthritis (clinicalTrials. Graul et al. IMMUNOMODULATORS & AGENTS FOR IMMUNIZATION In late 2012. and has been approved for the reduction of signs and symptoms of rheumatoid arthritis in adults since 2001. the FDa approved swedish orphan Biovitrum (sobi)’s Kineret® (anakinra) for the treatment of children and adults with neonatal-onset multisystem inflammatory disease (NoMID). In the 47 patients with an objective response. limited range of motion and bone fractures. ucB immediately began marketing certolizumab in the u. sobi acquired the product from amgen for development and commercialization worldwide. In september. canakinumab was approved in the u. gcTB is a rare and usually noncancerous tumor that destroys normal bone as it grows. The approval was based on data from the RaPID-Psa study. are not tolerated.s. unresectable. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 objective response rate of the 187 patients evaluated was 25%. randomized. double-blind. 145 were treated for at least 1 year. the 67 . has orphan drug designation for gcTB. In June 2013. comprising adults with severe active ankylosing spondylitis who have had an inadequate response to or are intolerant to NsaIDs and adults with severe active axial spondyloarthritis without radiographic evidence of ankylosing spondyloarthritis but with objective signs of inflammation by elevated cRP and/or MRI.s. shortly thereafter. traindicated. and in whom repeated courses of corticosteroids are not appropriate. In the month of May. Xgeva. In February. in July 2013. fatigue and pyrexia. 90% of these deaths occur in asia. FDa approved the first quadrivalent influenza vaccine. another new vaccine from Bharat Biotech. the u. mainly in children under 5 years of age. as FluenzTM Tetra. which involves the genera68 A. Ighy. In the tolerability assessment of hyQvia. 10%) and recombinant human hyaluronidase. Jenvac™.u.s.000 and 600. Graul et al.000 deaths and more than 20 million illnesses each year. Flublok was launched in the u. This novel vaccine does not use the influenza virus or eggs in its production. was launched last year in India. Meningococcal disease is a leading cause of bacterial meningitis. which contains both B strains and was designed to take the guesswork out of the B component. vaccines were available to help protect against a. and is plagued with various drawbacks. The vaccine is based on a JE strain isolated in Kolar. Baxter launched hyQvia in germany. In 2012.200 healthy volunteers. solution for subcutaneous use) as a replacement therapy for adult patients with primary and secondary immunodeficiencies. which is below the required efficacy threshold of 1.gov Identifier NcT00814320) that evaluated the safety and effectiveness of hyQvia in the prevention of acute serious bacterial infections. The rate of validated acute serious bacterial infections in the study was 0. This and three other new quadrivalent vaccines (glaxosmithKline’s Fluarix® Quadrivalent and FluLaval® Quadrivalent and sanofi Pasteur’s Fluzone® Quadrivalent) were all launched in the u. In studies involving approximately 1. non-controlled. In clinical trials. congenital agammaglobulinemia. which facilitates the dispersion and absorption of the Igsc. with five new influenza vaccines reaching the market and the first approval worldwide of the first vaccine for MenB disease.s. Typhoid fever causes between 250. approximately 50. c. X-linked agammaglobulinemia.ThE YEaR’s NEW DRugs & BIologIcs 2013 humoral immune defect in common variable immunodeficiency (cVID). The product is a new combination incorporating human normal immunoglobulin (Igsc.s. seroconversion was defined as a four-fold increase in serum Igg responses. FluMist® Quadrivalent (MedImmune).025 per patient per year. a Vero cell-derived purified inactivated Japanese encephalitis (JE) vaccine from Bharat Biotech. it also induced seroconversion in 92% of those aged 15-45 years.u. In addition to reducing disease burden. was also approved and launched last year in India. In December 2013. the u. 50(1) . according to the Who. The vaccine was safe and well tolerated in all age groups tested. B. about 1 ThoMsoN REuTERs – Drugs of Today 2014. In the area of influenza vaccines. in February 2013.I. Five main groups of meningococcal bacteria (a.0. Jenvac will decrease India’s reliance on imported JE vaccines. in addition to other new immunizing agents. Influenza vaccines have traditionally employed two influenza a strains plus one of two possible influenza B strains. most significantly the time required to produce sufficient amounts of the vaccine. It will replace the Fluenz trivalent vaccine from the 2014-2015 flu season onwards. antiquated and inefficient. open-label. Jenvac showed superior safety and immunogenicity as compared to the live sa14-14-2 vaccine. the European commission granted Baxter marketing authorization in all E. the novelty was the introduction for the first time in 2013 of quadrivalent vaccines. W-135 and Y. the typhoid conjugate vaccine Typbar-TcV™. Karnataka during the early 1980s that is purified and inactivated using the company’s advanced bioreactor technology. member states for the use of HyQvia (hyQ. making it the leading cause of viral encephalitis in the region. The application was based on results from a prospective. In May. in time for the 2013-2014 flu season. but not against disease caused by meningococcal B (MenB) bacteria. headache. c. another drawback of traditional influenza vaccines is their method of production. the most frequently reported adverse reactions were infusion site reactions. its first market. W-135 and Y) cause the majority of all cases around the world. The fourth-generation vaccine was designed to overcome two important limitations of previous vaccines: the lack of long-term protection and efficacy in children under the age of 2 years. In January. Tpybar-TcV induced seroconversion in 98% of infants aged 6-24 months and in 99% of children aged 2-15 years. FDa approved Flublok® (Protein sciences). 2013 was an active year for vaccines. In the past.s.000 cases of JE are reported each year in asia —although the disease is known to be vastly underreported—. This technology is complex. tion of viral strains in embryonated chicken eggs. the MedImmune intranasal vaccine was approved in the E. the first trivalent influenza vaccine made using an insect virus (baculovirus) expression system and recombinant DNa technology. Wiskott-aldrich syndrome and severe combined immunodeficiencies. and the pharmacokinetic parameters compared to immunoglobulin administered intravenously. MenB is a potentially deadly disease which is easily misdiagnosed and can kill within 24 hours of onset. multicenter phase III trial (clinicalTrials. the FDa also approved the mitogen-activated protein (MaP) kinase kinase (MEK1/MEK2) inhibitor trametinib dimethyl sulfoxide (Mekinist™. approximately 85% have V600E and approximately 10% have V600K mutations. glaxosmithKline) was approved by the u.. indicated as a single agent for the treatment of adults with hER2-positive. therascreen® EGFR RgQ PcR Kit. The authorization includes all 27 European union member states.s. poliomyelitis and invasive infections caused by H. The Raf kinase B inhibitor dabrafenib mesilate (Tafinlar®. In the u. Trastuzumab emtansine is indicated as a single agent for the treatment of patients with hER2-positive metastatic breast cancer who previously received trastuzumab and a taxane. The approval of Novartis’s Bexsero® (meningococcal group B vaccine [rDNA. In July 2013.u. where it will be marketed by chugai. government. the u. TREATMENT OF CANCER Trastuzumab emtansine (Kadcyla™. hexyon™. among patients with metastatic melanoma. including people with weakened immune systems (people diagnosed with hIV or atopic dermatitis). FDa in May 2013 for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDa-approved test. The two 69 . a new combination DTaP-IPV-Hib-HepB vaccine from sanofi Pasteur. 6-in-1 pediatric vaccine. Roche). influenzae type b. pertussis. FDa for use in children aged 6 weeks through 18 months. The conjugate vaccine was approved by the u. the European commission granted marketing authorization for Bavarian Nordic’s third-generation smallpox vaccine Imvanex®.s. strategic National stockpile under a contract with the u. among patients with Nsclc. The vaccine is indicated for active immunization against invasive disease caused by Neisseria meningitidis serogroup B strains and can be used in infants as young as 2 months. indicated for active immunization against smallpox disease for the general adult population. glaxosmithKline) for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E and V600K mutations as detected by an FDa-approved test. on the same day. as well as Iceland. Tafinlar and Mekinist were launched by gsK shortly after approval.K. Patients should have either received prior therapy for metastatic disease. adsorbed]) in the E. The antibody– drug conjugate was approved in september in Japan. its first market. ready-to-use. c and Y are responsible for most cases of meningitis in the u. the smallpox vaccine is being developed and supplied for emergency use to the u. which is able to determine whether a patient has either of these mutations in the BRAF gene. in January 2013 and in australia in august thus represents a significant development.s. reducing the number of injections and vaccination visits required for appropriate immunization of infants. for the treatment of receptor tyrosine-protein kinase erbB-2 (hER2)-positive inoperable or recurrent breast cancer. in July. also approved and launched last year was glaxosmithKline’s Menhibrix® (meningococcal groups C and Y and Haemophilus b tetanus toxoid conjugate vaccine). approximately half have a BRAF mutation. The vaccine is indicated for primary and booster vaccination of infants from 6 weeks of age against diphtheria. meningitidis serogroups B. was approved in the E.A.s. Graul et al. between 10 and 15% of caucasians and approximately 40% of asians have EGFR mutations. hepatitis B. in april 2013 and launched in germany. Boehringer Ingelheim worked in collaboration with Qiagen to develop the companion diagnostic test. separately or in combination. It was also approved in November by the European commission.I.u. FDa approved Boehringer Ingelheim’s afatinib (gilotrif™) as a first-line treatment for patients with metastatic non-small cell lung cancer (Nsclc) with common epidermal growth factor receptor (EGFR) mutations as detected by an FDa-approved test. was approved by the FDa in February 2013 and launched later that quarter. The FDa also granted premarket approval for bioMérieux’s companion diagnostic ThxID™-BRaF. In august. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 antibody trastuzumab and the antimitotic agent DM1 joined together via a stable linker. a novel antibody–drug conjugate incorporating the anti-hER2 ThoMsoN REuTERs – Drugs of Today 2014. meningitidis serogroups c and Y and Haemophilus influenzae type b. separately or in combination. component.. N. or developed disease recurrence during or within 6 months of completing adjuvant therapy. tetanus. germany and Ireland during the fourth quarter of 2013. in 10 of those who contract the disease will die despite appropriate treatment. Novartis launched Bexsero in the u. It is the first and only fully liquid.s. of those with BRAF V600 mutations. liechtenstein and Norway. The vaccine was also approved (as Imvamune®) in canada in November.s. unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane.s. to protect against invasive disease caused by N. Its efficacy was demonstrated in the luX-lung 3 trial.s. Roche) was approved and launched in the u. the FDa granted obinutuzumab Breakthrough Therapy Designation in May 2013 and priority review status in July. in January.1 months. and has orphan drug status for this indication.s. another targeted therapeutic also reached its first market last year: Exelixis’s cabozantinib S-malate (cometriq™). obinutuzumab (gazyva™. FlT-3. The drug is an inhibitor of multiple receptor tyrosine kinases. one of the largest phase III trials ever conducted in the setting of first-line EGFR mutationpositive. in January 2013. account for 90% of all EGFR mutations in Nsclc. 50(1) .s. the FDa requested that ariad suspend marketing of ponatinib. among patients treated with afatinib in this study. angiogenesis and maintenance of the tumor microenvironment. indicated in combination with chlorambucil chemotherapy for the treatment of patients with previously untreated chronic lymphocytic leukemia (cll). versus 6. -2 and -3.2% achieved a partial response or better in the pomalidomide plus low-dose dexamethasone arm compared to 7. the multikinase inhibitor ponatinib (Iclusig™. In February 2013. aXl and TIE-2.s. It is indicated for the treatment of progressive. VEgFR-1. of the 221 patients who were evaluable for response. Trk-B. spectrum Pharmaceuticals) was launched 70 A. Talon and its product portfolio were acquired by spectrum Pharmaceuticals in July 2013. Ponatinib was also approved for the treatment of Ph+ acute lymphoblastic leukemia (all) that is resistant or intolerant to prior TKI therapy. ariad Pharmaceuticals) was approved by the FDa. 29. afatinib is an orally active kinase inhibitor that is designed to bind and irreversibly inhibit EgFR (c-ErbB-1). Met. pending updates to the product’s prescribing information and implementation of a risk mitigation strategy.6 months.4 months. Graul et al. The overall response rate was based on responses assessed by the Independent Review adjudication committee based on the European group for Blood and Marrow Transplantation criteria. In December 2012.4% in the pomalidomide alone arm. Del19 and l858R. a randomized. in september 2013. and have demonstrated disease progression on or within 60 days of completion of the last therapy. median progression-free survival was 13. It is indicated for the treatment of adult patients with chronic.. accelerated or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (cMl) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. locally advanced or metastatic Nsclc. on the basis of the significance of positive progression-free survival results in phase III trials and the seriousness and life-threatening nature of the disease it is designed to treat. metastasis. The antimitotic agent sphingosomal vincristine (Marqibo®. more than a year after receipt of marketing approval. Ponatinib has orphan drug status for both indications. obinutuzumab was the first medicine to be approved with the FDa’s Breakthrough Therapy Designation. spectrum launched Marqibo shortly thereafter. among afatinib-treated patients who had the most common EGFR mutations (Del19 and l858R). open-label phase II study evaluating pomalidomide plus low-dose dexamethasone versus pomalidomide alone in patients with relapsed multiple myeloma who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib..s. afatinib was launched in the u. hER2 (c-ErbB-2) and c-ErbB-4 receptors. Discovered and developed by Talon Therapeutics. metastatic medullary thyroid cancer.ThE YEaR’s NEW DRugs & BIologIcs 2013 most common mutations. for the first time last september. where it has orphan drug status for the approved indication. Marqibo was approved in the u. It attacks targeted cells both directly and by working in conjunction with the body’s immune system. while the median had not yet been reached for the pomalidomide alone arm at the ThoMsoN REuTERs – Drugs of Today 2014. including lenalidomide and bortezomib. Obinutuzumab is a new monoclonal antibody designed to bind to cD20. which are involved in both normal cellular function and pathological processes such as oncogenesis. supporting the approval were the results of MM-002. including Ret. however later in the year. The median duration of response for patients in the pomalidomide plus low-dose dexamethasone arm was 7.s. in august 2012 for the treatment of adult patients with Philadelphia chromosome-negative (Ph–) all in second or greater relapse or whose disease has progressed following two or more antileukemia therapies. a protein found only on B cells. the median progression-free survival was 11. the u. launched in the u. on the basis of increasingly frequent postmarketing reports of serious and life-threatening blood clots and severe narrowing of blood vessels in patients treated with the drug. and was launched in the u.I. its first market. FDa approved celgene’s pomalidomide (Pomalyst®) for the treatment of multiple myeloma in patients who have received at least two prior therapies.9 months for those treated with pemetrexed and cisplatin. The company complied with this request and is now working with the agency to resume marketing of the drug.. In November 2013. a total of 219 patients were evaluable for safety. selective and covalent inhibitor of the enzyme Tyrosine-protein kinase BTK (Bruton tyrosine kinase). two second messengers that regulate certain downstream proteins during B-cell signaling. later in the first quarter. Pomalidomide is an immunomodulatory derivative of thalidomide (IMiD) and is contraindicated in pregnancy. algeta and development and marketing partner Bayer schering Pharma launched radium Ra 223 dichloride (Xofigo®) in the u. it also has orphan drug status for the indication of Mcl. which plays an essential role in B-cell maturation and mast cell activation. The BTK inhibitor ibrutinib (Imbruvica™) was approved and launched in the u. respectively. 50(1) 71 . Ibrutinib was discovered by Pharmacyclics and was licensed to Janssen in 2011 for codevelopment and comarketing worldwide. 9). diffuse large B-cell lymphoma and relapsed or refractory mantle cell lymphoma. In May 2013. with 17% of patients achieving a complete response and 49% achieving a partial response. The approval of ibrutinib was based on the favorable overall response rate (oRR) and duration of response (DoR) seen in the phase II study PcYc-1104. and was approved by the European commission in august. The most common grade 3 or 4 adverse reactions (15%) in the pomalidomide plus low-dose dexamethasone arm versus pomalidomide alone.4. The agent is a radiopharmaceutical incorporating the alpha particle-emit- Figure 9.A. anemia (21 and 22%). This leads to the hydrolysis of PIP2 into inositol triphosphate (IP3) and diacylglycerol (Dag). and is indicated for use in treating B-cell malignancies such as small lymphocytic lymphoma. The median DoR was 17. ThoMsoN REuTERs – Drugs of Today 2014. ibrutinib has Breakthrough Therapy Designation from the FDa.s. which results in the phosphorylation of phospholipase c. which enrolled 111 patients with relapsed or refractory Mcl. Ibrutinib functions as an orally available. Graul et al.8% oRR. like obinutuzumab. time of approval. Bruton tyrosine kinase (BTK) is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival of malignant B cells (Fig. The efficacy results of this study demonstrated a 65.5)-trisphosphate (PIP3). were neutropenia (38 and 47%). BTK is characterized by a Ph domain that selectively binds to phosphatidylinositol (3. It is only available through the Pomalyst Risk Evaluation and Mitigation strategy (REMs) program.I.s. It was launched in the u.s. thrombocytopenia (19 and 22%) and pneumonia (23 and 16%).5 months. in 2013 for the treatment of ThE YEaR’s NEW DRugs & BIologIcs 2013 mantle cell lymphoma (Mcl). .ThE YEaR’s NEW DRugs & BIologIcs 2013 ting isotope radium 223. cambodia.s.. laos. three major components of the vitreoretinal interface that play an important role in VMa. Iluvien® (fluocinolone acetonide intravitreal implant in applicator) is a sustained-release intravitreal implant developed by alimera sciences under license from psivida to treat vision impairment associated with chronic diabetic macular edema considered insufficiently responsive to available therapies. Bone metastases are particularly prevalent among men with prostate cancer. as well as in Brunei. Racotumomab could provide an alternative treatment for lung cancer patients. Tafluprost is a prostaglandin F2α analogue that promotes the outflow of aqueous humor. an antiganglioside. an NDa continues under review in the u. ThoMsoN REuTERs – Drugs of Today 2014.I.000 people worldwide. and it also holds the potential to be studied and applied to other tumor types that have the same target. The product was developed by alcon. and was introduced later in the year in germany. The vaccine has been licensed in 25 countries on the american and asian continents under the name Vaxira. cystinosis is a genetic lysosomal storage disease that affects approximately 300 children and young adults in the u. was launched for the first time last year in argentina. Each implant provides a therapeutic effect of up to 36 months by delivering sustained submicrogram levels of fluocinolone acetonide. singapore. It is the first and only alpha particle-emitting radioactive therapeutic agent approved by the agency that has demonstrated improvement in overall survival and delay in time to first symptomatic skeletal event compared to placebo. a fixed-dose combination product for the treatment of glaucoma. another combination product for glaucoma. anti-idiotypic antibody-based cancer vaccine from REcoMBIo. which allows for a self-sealing wound. is a selective proteolytic enzyme that cleaves fibronectin. and is approved by the FDa for the treatment of patients with castration-resistant prostate cancer. and timolol is a β-adrenoceptor blocker that inhibits the production of aqueous humor. when untreated. Racotumomab (Vaxira®). frequently leads to retinal distortion. It is indicated for the treatment of advanced-stage Nsclc in patients undergoing chemotherapy and radiotherapy or in patients who have not responded to first-line therapy. affecting up to 90% of these patients. administered by intravitreal injection to the affected eye. 50(1) .K. ocriplasmin. Taiwan and India. and some 2. that does not include a β-blocker. kidneys. Thailand and the Philippines. and has indicated that results from a new clinical trial will need to be submitted. Thrombogenics announced the u. further deterioration in vision and irreversible damage to eyesight. and brimonidine tartrate. with Elea laboratories having the exclusive right to sell it in argentina and Eurofarma having the exclusive license in Brazil. Iluvien was launched for the first time last april in the u. simbrinza is the only fixed-dose combina72 A.s. symptomatic bone metastases and no known visceral metastatic disease. It is injected in the back of the patient’s eye to a position that takes advantage of the eye’s natural fluid dynamics. symptomatic VMa is a progressive sight-threatening condition that. including the corneas. as it implies less toxicity and side effects compared to conventional cancer therapies. where it tripled the 2-year survival rate among patients receiving treatment. pancreas. an α2-adrenoceptor agonist. where the FDa has issued a complete response letter expressing concerns regarding the benefit-to-risk and safety profiles of Iluvien. It causes cystine crystals to build up in various organs of the body. The applicator employs a 25-gauge needle. launch of ocriplasmin (Jetrea®) for the treatment of symptomatic vitreomacular adhesion (VMa). santen’s TaPcoM (tafluprost/timolol maleate). the global eye care division of Novartis. was approved last year in Japan for the treatment of glaucoma and ocular hypertension. OPHTHALMIC DRUGS simbrinza™ (brinzolamide/brimonidine tartrate). Graul et al.s. as well as in Europe. and have a significant negative impact on mortality and quality of life. Innogene Kalbiotech has the license to market the drug in Korea. Its active components are brinzolamide. and is indicated for the reduction of elevated intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension. The vaccine has shown significant results in the clinical setting. REcoMBIo holds the license in the rest of the american and asian countries. as well as semi-exclusive rights in the rest of the south american continent. was approved and launched for the first time last year in the u. In the early days of January 2013. laminin and collagen. tion therapy for glaucoma in the u. Racotumomab has also been approved in cuba. a carbonic anhydrase inhibitor.s. Myanmar. liver. muscles. it is also approved in several other European countries.s. Indonesia. Malaysia. the combination of ezetimibe and ThoMsoN REuTERs – Drugs of Today 2014. double-blind. Graul et al. In 2013. two new products developed to treat this disorder —both fist-in-class agents— reached the market for the first time. comprising not less than 96% EPa (ethyl eicosapentaenoic acid) in a 1-g capsule. where it is indicated as an adjunct to low-fat diet and other lipid-lowering treatments. placebo-controlled study in which 628 patients with hyperlipidemia were treated for up to 12 weeks. Merck & co. as an adjunct to other lipidlowering treatments or if such treatments are unavailable. In a multicenter. aegerion) was launched in the u. The product is also indicated for the reduction of elevated total cholesterol and lDl cholesterol in patients with homozygous familial hypercholesterolemia.’s liptruzet™ (ezetimibe/atorvastatin) was approved and launched last year in the u. saroglitazar was launched in India during the third quarter.s. and an increase in hDl cholesterol. The NDa for saroglitazar was based on a comprehensive clinical development program spanning 8 years. METABOLIC DRUGS amarin launched Vascepa® (icosapent ethyl ester) in the u.s. launched cystaran™ (cysteamine ophthalmic solution) last May in the u. having previously granted it orphan drug designation. was approved by the European commission in august 2013. The ultrapure omega-3 fatty acid product. corneal haziness and photophobia. the agent led to a reduction in triglycerides and in lDl cholesterol. 73 .I. the combination drug lowered lDl cholesterol across all doses by more than 50%. homozygous familial hypercholesterolemia (hoFh) is a serious. indicated to treat severe hypertriglyceridemia (triglyceride ≥ 500 mg/dl). In published controlled trials. for the treatment of elevated lDl cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough.s. occurring in only 1 per million (source: Fh Foundation). in January 2013. foreign body sensation. In January the microsomal triglyceride transfer protein (MTTP) inhibitor lomitapide (Juxtapid™. The FDa approved cysteamine in october 2012. occurring in 1 in 300-500 individuals worldwide. While heterozygous Fh is relatively common.s. amarin filed a supplemental NDa for Vascepa for use as an adjunct to diet in the treatment of adult patients with high triglycerides (Tg ≥ 200 mg/dl and < 500 mg/dl) with mixed dyslipidemia and coronary heart disease (chD) or a chD risk equivalent (the aNchoR indication). Patients with the disorder often develop premature and progressive atherosclerosis. More than 80% of all diabetic patients are believed to have dyslipidemia —a potential market of up to 300 million patients worldwide. including squinting. rare genetic disease that impairs the function of the receptor responsible for removing lDl cholesterol from the body. however. Pooled across doses. a part of the sigmaTau group Rare Disease Franchise. In June. was approved by the FDa in July 2012. while displaying a tolerability and safety profile similar to that of placebo. the cystinosis Research Foundation and the cystinosis Research Network.. change in visual acuity. cholib is indicated as adjunctive therapy to diet and exercise in high cardiovascular risk adult patients with mixed dyslipidemia to reduce triglycerides and increase hDl cholesterol levels when lDl cholesterol levels are adequately controlled with the corresponding dose of simvastatin monotherapy. Results from the first phase III program of saroglitazar. sigmaTau developed the cystine-depleting agent in partnership with the National Institutes of health and in cooperation with the cystinosis Foundation. sigma-Tau Pharmaceuticals. brain and white blood cells. as well as a reduction in fasting plasma glucose and glycosylated hemoglobin (hba1c). another statin-containing combination product.A. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 atorvastatin reduced lDl cholesterol by a mean 56% compared with 44% for all atorvastatin doses pooled. abbott’s cholib (fenofibrate/simvastatin).. Vascepa significantly reduced triglyceride levels without elevating lDl cholesterol levels. had been approved for marketing in India. hoFh is much more rare. an FDa advisory committee recently voted against the approval of this new indication. The accumulation of cystine crystals in the cornea can lead to a range of ocular complications. Zydus reported that saroglitazar (lipaglyn™). the combination tablet has been shown to be bioequivalent to coadministration of corresponding doses of ezetimibe and atorvastatin. Based on this and other clinical studies. a novel peroxisome proliferator-activated receptor (PPaR) agonist indicated for the treatment of diabetic dyslipidemia or hypertriglyceridemia in type 2 diabetes not controlled by statins alone. using pioglitazone as a comparator drug in patients with diabetes. a loss of lDl receptor function results in extreme elevation of blood cholesterol levels. where it is indicated for the treatment of corneal cystine crystal accumulation in patients with cystinosis. later in the year. showed that at a dose of 4 mg. who were main- Figure 10. When added to baseline lipid-lowering therapy. mipomersen sodium (Kynamro™). including 7 patients aged 12-16 years. marks mTTP inhibitors such as lomitapide as potential monotherapy for reducing lDl cholesterol as well as triglycerides.I.s. the product carries a black box warning and is available only through a Risk Evaluation and Mitigation strategy (REMs) program. total cholesterol and non-hDl cholesterol in patients with hoFh. to reduce lDl cholesterol.ThE YEaR’s NEW DRugs & BIologIcs 2013 including lDl apheresis where available. placebo-controlled. 74 ThoMsoN REuTERs – Drugs of Today 2014. The approval of lomitapide was based on a pivotal phase III study that evaluated the safety and effectiveness of the drug in reducing lDl cholesterol levels in 29 adult patients with hoFh (clinicalTrials. The randomized. with or without lDl A. Mipomersen is an antisense oligonucleotide that blocks the production of apolipoprotein B-100. approval was based on the largest clinical trial conducted to date in the hoFh patient population. Therefore. inhibiting MTTP results in a reduction of cholesterol and triglyceride blood levels by limiting the production of lipoproteins from the intestine and liver. in adult patients with hoFh. total cholesterol. In august. lomitapide significantly lowered lDl cholesterol levels from 336 mg/dl to 190 mg/dl. as well as Japan. This mechanism of action. double-blind. during the first quarter. was approved and launched in the u. Graul et al. a decrease of approximately 40%.gov Identifier NcT00730236). 50(1) . lomitapide acts as a microsomal triglyceride transfer protein (MTTP) inhibitor and is useful as a treatment option for lipoprotein disorders such as homozygous familial hypercholesterolemia. together with an ability to suppress apolipoprotein B-containing lipoproteins from both intestinal and hepatic sources. the European commission granted approval to lomitapide (known there as lojuxta™) as an adjunct to low-fat diet and other lipidlowering medicinal products. lomitapide has orphan drug status for this indication in the u. apolipoprotein B. apolipoprotein B and nonhDl cholesterol in patients with hoFh (Fig. 11). Because of the risk of liver toxicity. The second drug for hoFh. It is approved as an adjunct to lipid-lowering medications and diet to reduce lDl cholesterol. 10). the protein that provides the structural core for atherogenic particles such as lDl (Fig. multicenter trial enrolled 51 patients aged 12-53 years. MTTP promotes the formation and secretion in the liver of very low-density lipoprotein (VlDl) cholesterol. apheresis.s. or between mipomersen and simvastatin or ezetimibe.7%). which are both implicated in the development of cardiovascular disease. Graul et al. Mipomersen sodium selectively targets apolipoprotein B (apoB). a protein crucial to the synthesis and transport of lDl and VlDl cholesterol.4%). or 25%. The most common adverse reactions in patients treated with mipomersen that led to treatment discontinuation and occurred at a rate greater ThE YEaR’s NEW DRugs & BIologIcs 2013 than placebo were injection-site reactions (5. Kynamro carries a boxed warning citing the risk of hepatic toxicity. alanine aminotransferase (alT) increase (3. ThoMsoN REuTERs – Drugs of Today 2014. Treatment with mipomersen further reduced lDl cholesterol levels by an average of 113 mg/dl. double-blind. the FDa approved the selective 5-hT2c receptor agonist lorcaserin hydrochloride (Belviq®. Data showed that 18% of patients on mipomersen and 2% of patients on placebo discontinued treatment due to adverse reactions. the first prescription weight loss treatment Figure 11.I. of whom 261 patients received mipomersen and 129 patients received placebo for a median treatment duration of 25 weeks. arena).A. safety data were based on pooled results from 4 randomized. In June 2012. Mipomersen sodium is a second-generation antisense oligonucleotide which is indicated for use in treating conditions such as homozygous familial hypercholesterolemia. placebo-controlled phase III trials with a total of 390 patients. Its potential for lowering cholesterol and triglyceride levels is thus expected to be of use in the prevention and management of cardiovascular disease and lipoprotein disorders. and also reduced all measured endpoints for atherogenic particles.5%). aspartate aminotransferase (asT) increase (2. The product was discovered by Isis Pharmaceuticals and was licensed to genzyme for development and commercialization. The 10 central 2’-deoxynucleotides serve as the site for RNase hmediated mRNa degradation. taining a regimen of maximally tolerated lipid-lowering medications. flu-like symptoms (2. No clinically relevant pharmacokinetic interactions were reported between mipomersen and warfarin. The drug selectively targets apoB by hybridizing within the coding region of apoB-100 mRNa. 50(1) 75 . from a treated baseline of 439 mg/dl. Mipomersen sodium is a synthetic phosphorothioate oligonucleotide sodium salt with five 2’-O-methoxyethyl modifications (2’-MoE) at the 2’ position of the ribose on both 3’ and 5’ ends.0%).3%) and abnormal liver function test (1. It has orphan drug status for the hoFh indication. which is manufactured by arena at its facility in switzerland. to orphan medical products for which the applicant is able to demonstrate that the active substance has been in well-established medicinal use within the E. glycerol phenylbutyrate has orphan drug status for this indication in the u.c..g. Throughout their lives. Bristol-Myers squibb is codeveloping metreleptin through its diabetes alliance with astraZeneca and the product has priority review status. The European commission in 2011 refused to grant approval for orphacol. was launched for the first time in Japan. placebo-controlled trials that included nearly 8. a subsidiary of Bristol-Myers squibb. specifically. cetilistat is the first therapy that controls lipid absorption approved in Japan for the treatment of obesity with complications. hypertriglyceridemia. Graul et al. an FDa advisory committee voted 11-1 in favor of approving metreleptin for the treatment of pediatric and adult patients with generalized lipodystrophy. last year the European commission granted a marketing authorization.ThE YEaR’s NEW DRugs & BIologIcs 2013 approved in the u.s. uct was approved by the Japanese Ministry of health. like the marketed drug orlistat. which has orphan drug status. 50(1) . and blocks the absorption of fat from the gut. The drug was discovered by alizyme. however. a lipolytic enzyme secreted by the digestive tract and pancreas. such as severe diabetes.I. for at least 10 years. laboratoires cTRs). lorcaserin was launched in the u. Xanthine oxidase inhibitors block the production of uric acid by selectively and reversibly suppressing xanthine oxidoreductase within the purine metabolic pathway. with and without type 2 diabetes. with recognized efficacy and an acceptable level of safety. hepatic steatosis and steatohepatitis (also known as fatty liver disease). In the u. paving the way for the september approval of orphacol by the E. The product. congenital lipodystrophy is a rare and life-threatening disorder characterized by a lack of the subcutaneous fat tissue required for normal metabolic functions. such as hypertension. type 2 diabetes or dyslipidemia. the product is indicated for use in addition to diet and exercise in adults who are obese (BMI ≥ 30 kg/m2) or who are overweight (BMI ≥ 27 kg/m2) and have at least one weight-related condition. arginine. The xanthine oxidase inhibitor topiroxostat was approved and launched last year in Japan for the treatment of gout and hyperuricemia. treated for 52-104 weeks. urea cycle disorders (ucDs) are a collection of inherited metabolic disorders characterized by high levels of systemic ammonia. valid throughout the European union. last year the FDa approved hyperion Therapeutics’ Ravicti™ (glycerol phenylbutyrate).s. Takeda has held development and commercialization rights in Japan since 2003. and is highly correlated to metabolic abnormalities. in 13 years. Eisai is responsible for marketing and distribution of lorcaserin. The safety and efficacy of lorcaserin were evaluated in 3 randomized. a potential neurotoxin.s. another antiobesity agent was approved last year for the first time in Japan: the triacylglycerol lipase inhibitor cetilistat (oblean®). This results in decreased body weight. citrulline. Norgine acquired all rights to cetilistat in october 2009..000 patients who were obese or overweight. Zeria Pharmaceutical launched Phosribbon® combination granule (INKP-102. to urea. protein-free calorie supplements). is indicated as a treatment for inborn errors in primary bile acid synthesis due to 3β-hydroxy-Δ5-c27-steroid oxidoreductase deficiency or Δ4-3-oxosteroid-5β-reductase deficiency in infants. through a series of enzymatic steps. cetilistat inhibits the activity of lipase. patients with ucDs may experience recurrent hyperammonemic crises in which ammonia levels rise. the former markets the product under the name uriadec® and the latter under the name Topiloric®. In December. Topiroxostat was codeveloped by sanwa Kagaku Kenkyusho and Fuji Yakuhin. essential amino acids. ammonia is produced via normal protein ingestion. and can develop complications ranging from nausea. monobasic sodium phosphate ThoMsoN REuTERs – Drugs of Today 2014. This product was approved by way of a simplified procedure that is applicable. the body normally detoxifies it by converting it. which is secreted in urine. vomiting and headache. The prod76 A. inter alia. to coma and death. reduced visceral fat and improved parameters related to lifestyle disease. in June. shionogi developed metreleptin for the Japanese market under license from amylin. last year metreleptin (recombinant human oB protein). children and adolescents aged 1 month to 18 years and in adults. for cholic acid (orphacol. labour and Welfare in March and was launched in July. the first drug developed specifically to treat congenital lipodystrophy.u.s. where it has orphan drug status. a nitrogen-binding agent indicated for the chronic management of ucDs in patients aged 2 and older whose disease cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Following receipt of DEa scheduling in May 2013. in July 2013 the European general court annulled that decision. Ravicti must be used with dietary protein restriction and in some cases dietary supplements (e. In March 2013. indicated for the reduction of alcohol consumption in adult patients with alcohol dependence. human extracellular proteins and allogeneic human dermal fibroblasts. the u. botulinum toxin has been identified in the u. under the new European approval. It was launched in its first European markets (Norway. a radioactive 77 .A.s. studies have demonstrated that the cell-based product secretes human growth factors and other proteins that are known to be involved in wound repair and regeneration. It is supplied as a cellular sheet that is applied to a surgically created vascular wound bed. D.s. defined as over 60 g/day for men and over 40 g/day for women.s. Phosribbon is usually used for the treatment of hypophosphatemia in combination with an activated vitamin D agent.s. was launched for the first time last year in the u. It was developed with support from the Biomedical advanced Research and Development authority within the u. These results provided substantial evidence that the antitoxin is reasonably likely to benefit humans with botulism. DIAGNOSTIC AGENTS In october.000 patients with alcohol dependence. which has orphan drug designation from the FDa. which permits demonstration of efficacy in appropriate animal models when it is not feasible or ethical to conduct efficacy studies in humans. B. cangene began shipping Bat to the u. The effectiveness of the product was studied under the FDa’s animal Rule. c. Graul et al. subjects treated with nalmefene showed a 40% reduction in total alcohol consumption within the first month and an approximately 60% reduction after 6 months. BioTie Therapies/lundbeck) in February 2013. a novel wound-healing agent developed by organogenesis. The safety of the product was tested in 40 healthy human volunteers and also monitored in 228 patients who received the antitoxin experimentally under a botulism treatment program administered by the cDc. FDa approved cangene’s Bat™ (botulism antitoxin [equine] heptavalent [A. It has been marketed since 2001 as a purgative agent for colon cleansing prior to colonoscopy.u. This is a new indication for nalmefene. Department of health and human services’ office of the assistant secretary for Preparedness and Response. D. which is dysregulated in patients with alcohol dependence. nalmefene acts on the brain’s motivational system. strategic National stockpile during the second quarter. 50(1) ThE YEaR’s NEW DRugs & BIologIcs 2013 botulism following documented or suspected exposure to botulinum neurotoxin subtypes a. While the specific way in which gintuit increases keratinized tissue has not been identified. the drug was shown to be effective in reducing alcohol consumption in patients with a high drinking risk level. F or g. and will be maintained in the strategic National stockpile and distributed through the centers for Disease control and Prevention (cDc) Drug service. last March in Japan. for the treatment of mucogingival conditions in adults. the product is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level. The marketing authorization applies to all 27 E. FDa approved gE healthcare’s Vizamyl™ (flutemetamol F18 injection). Nalmefene has been developed for use on an “as needed” basis. F. B.s. Due to its extreme potency and potential lethality. TREATMENT OF POISONING & DRUG DEPENDENCY The European commission approved selincro® (nalmefene. becoming the first oral phosphate to reach the market in that country. member states and is based on the results from 3 pivotal. Zeria developed this agent following requests from the Review committee on unapproved Drugs and Indications with high Medical Needs. without physical withdrawal symptoms and who do not require immediate detoxification. lundbeck intends to provide the drug as part of a novel treatment concept that includes continuous psychosocial support focused on the reduction of alcohol consumption and treatment adherence. placebo-controlled trials that evaluated the efficacy and safety of nalmefene in approximately 2. E. In these trials. Poland and the Baltic countries) in april. which was first launched by Baker Norton in 1995 for the treatment of opioid overdose. monohydrate/dibasic sodium phosphate anhydrous). C. Finland. is derived from horse plasma and contains a mixture of antibody fragments that neutralize all of the seven botulinum nerve toxin serotypes known to cause botulism. specifically. DENTAL AGENTS gintuit™ (allogeneic cultured keratinocytes and fibroblasts in bovine collagen). with one tablet taken each day when the patient feels a risk of drinking. doubleblind. The antitoxin. E. Phosribbon has orphan drug status in Japan for this indication. randomized. as one of the highest priority bioterrorism threats. G]) for the treatment of patients showing signs of ThoMsoN REuTERs – Drugs of Today 2014. a unique dual-acting opioid system modulator. the u. an oral agent for hypophosphatemia.s.I. The product is a bilayered structure composed of an upper cornified layer formed by allogeneic human keratinocytes and a lower layer formed by bovine-derived collagen. biocompatible polymer capsule containing c4.I. c4 Imaging). 50(1) . eliminating the need for computed tomography in the assessment of prostate brachytherapy. new combinations and important new formulations of previously marketed drugs). Vizamyl is an adjunct to other diagnostic evaluations. small-molecule radiopharmaceutical designed to identify the lymph nodes that drain from a primary tumor. Graul et al. for use in lymphatic mapping procedures that are performed to help in the diagnostic evaluation of potential cancer spread in patients with breast cancer and melanoma.s. Table II presents an overview of all new drugs and biologics launched in 2013. Vizamyl is the only PET imaging tracer for detection of amyloid approved by the FDa for visual interpretation of color images rather than black and white assessment. a unique MRI agent. lung/bronchus cancer. as part of Navidea’s u. including line extensions (new indications.ThE YEaR’s NEW DRugs & BIologIcs 2013 diagnostic agent indicated for positron emission tomography (PET) imaging of the brain to estimate β amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for alzheimer’s disease or other causes of cognitive decline.s. prostate cancer.s. Navidea plans to continue developing the product into other solid tumor areas that may include head and neck cancer. Products in this table are listed in alphabetical order. which have the highest probability of harboring cancer. colorectal cancer and others. The capsules are implanted as brachytherapy seed spacers that facilitate the anatomical localization of seeds using a single post-implant MRI procedure. cardinal health is responsible for the sale and distribution of the product to healthcare professionals through its existing network of nuclear pharmacies. receptor-targeted. FDa granted 510(k) approval for C4-ECAM (sirius™. Technetium Tc 99m tilmanocept is a novel. DISCLOSURES The authors state no conflicts of interest. In December. A. distribution partnership. c 78 ThoMsoN REuTERs – Drugs of Today 2014. Table III summarizes the estimated market size for selected products introduced last year. and will be commercially available in 2014. The sirius MRI Marker consists of a 5. Navidea Biopharmaceuticals launched lymphoseek® (technetium Tc 99m tilmanocept) injection last year in the u. thyroid cancer. the u. a novel positive-signal MRI marker developed for the localization of radioactive seeds used in brachytherapy of prostate cancer.5-mm sealed. 000 u for serotype F antitoxin.67 ml (100 mg) anakin. tablets.alogliptin benzoate/metformin hydrochloride*.I. prefilled syringe. 20.B. to treat adults (18 years or older) with multidrug–resistant pulmonary tuberculosis (TB) when other alternatives are not available Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation** as an adjunct to diet and exercise. 600 u for serotype D antitoxin. to improve glycemic control in adults with type 2 diabetes For topical (nonsubmerged) application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults First-line treatment of patients with metastatic non-small cell lung cancer (Nsclc) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (l858R) substitution mutations as detected by an FDaapproved test gintuit™ (us) afatinib.5 mg/1000 mg alogliptin/metformin hcl anakinra. tablets. New product intros – 2013.100 u for serotype E antitoxin. heptavalent. 30 & 40 mg Boehringer Ingelheim giotrif™ (us) Treatment of functional dyspepsia acotiamide hydrochloride hydrate. F or g in adults and pediatric patients toxin. Graul et al. codeveloped and comarketed by astellas acofide® (JP) Indication active ingredient2 company Trade name (country)1 Table II.5 mg/500 mg & 12. 5. c.000 u for serotype c antitoxin. topical gel. injection multisystem inflammatory disease (NoMID)** Bisoprolol fumarate. E. transdermal patch***.Treatment of children and adults with neonatal-onset ra in solution for s. 100 mg Zeria. 3. marketed and distributed by astellas cangene galderma Kazano® (us) Kineret® (us) Eliquis® (us) ThoMsoN REuTERs – Drugs of Today 2014. tablets. tablets.and Treatment of symptomatic botulism following documented 50-ml vials containing no less than 4. 3. and 600 u for serotype g antitoxin organogenesis Takeda swedish orphan BioVitrum Bristol-Myers squibb/Pfizer Janssen Therapeutics Toa Eiyo. tablets.c. 50(1) sirturo™ (us) Bisono® Tape (JP) BaT (us) Mirvaso® (us) Brimonidine tartrate. 0. A. cellular sheet for oral application. ThE YEaR’s NEW DRugs & BIologIcs 2013 79 . 12.300 u for serotype B anti. D. for serotype a antitoxin. approximately 4 million cells are initially used to manufacture the product Continued Topical treatment of persistent (nontransient) facial erythema of rosacea in adults 18 years of age or older** Mild to moderate essential hypertension as part of combination therapy. 0. 20.33% Bedaquiline. 2. 100 mg apixaban.5 & 5 mg allogeneic cultured keratinocytes and fibroblasts in bovine collagen. 3.500 units (u) or suspected exposure to botulinum neurotoxin subtypes a. 4 & 8 mg Botulism antitoxin (equine). 0%) and brimonidine tartrate (0.c. • control and prevention of bleeding episodes in adults with 1000.I. tablets. tablets. lyophilized powder in single-use Treatment of adult patients with active psoriatic arthritis** vials. and in whom repeated courses of corticosteroids are not appropriate** Treatment of active systemic juvenile idiopathic arthritis (sJIa) in patients aged 2 years and older** as an adjunct to diet and exercise.antihemophilic factor indicated for: der in single-use vials containing nominally 250. 10 & 25 mg coagulation factor IX (recombinant). 100 & 300 mg cabozantinib s-malate. are not tolerated. 200 mg.2%) active ingredient2 cimzia® (Eu) cimzia® (us) cimzia® (us) ucB Novartis Ilaris® (us) Ilaris® (DE. lyophilized pow. injection canagliflozin. capsules 20 & 80 mg Brinzolamide/brimonidine tartrate*.) New product intros – 2013. 50(1) Treatment of cataplexy in patients with narcolepsy** clomipramine hydrochloride.80 Treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom nonsteroidal anti-inflammatory drugs (NsaIDs) and colchicine are contraindicated. for reconstitution and s. metastatic medullary thyroid cancer Reduction of intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension Indication ThoMsoN REuTERs – Drugs of Today 2014. Graul et al. to improve glycemic control in adults with type 2 diabetes Treatment of progressive. 500. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. (Cont. single-use vials containing lyophilized powder. 200 mg/ml Treatment of adults with active akylosing spondylitis** canakinumab. or do not provide an adequate response. ocular suspension in multidose bottle. who have had an inadequate response to or are intolerant to NsaIDs** certolizumab pegol. PR) Continued Ttreatment of adult patients with severe active axial spondyloarthritis. for reconstitution with 1 ml sterile water for injection single-use prefilled syringes. brinzolamide (1. comprising adults with severe active ankylosing spondylitis who have had an inadequate response to or are intolerant to nonsteroidal anti-inflammatory drugs (NsaIDs) and adults with severe active axial spondyloarthritis without radiographic evidence of ankylosing spondyloarthritis but with objective signs of inflammation by elevated cRP and/or MRI. 2000 or 3000 Iu hemophilia B • Perioperative management in adults with hemophilia B • Routine prophylaxis to prevent or prevent or reduce the frequency of bleeding episodes in adults with hemophilia B alfresa Pharma Baxter anafranil® (JP) Rixubis (us. gR) Exelixis Janssen Therapeutics Invokana™ (us) alcon (Novartis) simbrinza™ (us) cometriq™ (us) company Trade name (country)1 Table II. 180 mg. . I. lDl-c. single-use vials containing sterilized. 120 & 240 mg Treatment of patients with relapsing forms of multiple sclerosis Dolutegravir. as an adjunct to other lipid-lowering treatments Primary and booster vaccination of infants from 6 weeks of age against diphtheria.collagenase Clostridium histolyticum. 10 mg/10 mg.9 mg. 1 g.c. hepatitis B.) New product intros – 2013.44%)*** symptomatic relief of noninfectious diarrhea in adult patients with hIV/aIDs on antiretroviral therapy Treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy** Treatment of hyperphosphatemia in adult patients with chronic kidney disease stage 5 receiving hemodialysis or peritoneal dialysis** colestilan. for reconstitution with supplied sterile diluent crofelemer. licensed from Napo sigma-Tau glaxosmithKline amgen Biogen Idec ViiV healthcare sanofi Pasteur Merck & co. to: • Reduce elevated total-c. 50(1) Xgeva® (us) Tecfidera™ (us) Tivicay® (us) hexyon™ (DE) liptruzet™ (us) Ezetimibe/atorvastatin*. for the treatment of hIV-1 infection in adults and children aged 12 years and older and weighing at least 40 kg Treatment of adults and skeletally mature adolescents with giant cell tumor of bone (gcTB) that is unresectable or where surgical resection is likely to result in severe morbidity** Treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDa-approved test cysteamine hydrochloride. tablets.4 mg/ml of cysteamine (0. Xiaflex® (us) Fulyzaq™ (us) cystaran™ (us) Tafinlar® (us) ThoMsoN REuTERs – Drugs of Today 2014. 10 mg/40 mg & 10 mg/80 mg DTaP-IPV-hib-hepB vaccine. tetanus. oral granules. capsules. A. 2 & 3g Mitsubishi Tanabe Pharma/NextPharma Indication BindRen® (DE. lyophilized powder. ThE YEaR’s NEW DRugs & BIologIcs 2013 81 . aT) active ingredient2 company Trade name (country)1 Table II. injection Dimethyl fumarate. 50 mg auxilium salix. 125 mg Dabrafenib mesilate.5 mg/ml of cysteamine hydrochloride patients with cystinosis** equivalent to 4. delayed-release tablets. sterile ophthalmic solution Treatment of corneal cystine crystal accumulation in containing 6.5 ml Continued as adjunctive therapy to diet. apo B. single-use vials. delayed-release capsules. (Cont. tablets. and to increase hDl-c in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia • Reduce elevated total-c and lDl-c in patients with homozygous familial hypercholesterolemia (hoFh). 0. 10 mg/20 mg. 120 mg/1. pertussis. vials and prefilled syringes. 0. poliomyelitis and invasive infections caused by Haemophilus influenzae type b In combination with other antiretroviral agents. 50 & 75 mg Denosumab. Graul et al. Tg and non-hDl-c.7 ml for s. film-coated tablets. ) New product intros – 2013. to reduce triglyceride (Tg) levels in adults with severe (Tg ≥ 50 mg/dl) hypertriglyceridemia** Treatment of patients with mantle cell lymphoma who have received at least one prior therapy golimumab.in adult patients who have demonstrated corticosteroid dose prefilled syringe. 1. inhalation capsules. dry powder inhaler. including chronic bronchitis and/or emphysema Fluocinolone acetonide.1 g/ml human normal immunoglobulin/recombinant human Replacement therapy in adults (≥ 18 years) in primary hyaluronidase*. once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (coPD). sustained-release intravitreal Treatment of vision impairment associated with chronic implant in applicator. single-dose prefilled smartJect® Treatment of moderately to severely active ulcerative colitis autoinjector. and severe combined immunodeficiencies Biotest Pharmaceuticals glaxosmithKline Bivigam™ (us) Fluarix® Quadrivalent (us) Continued Influenza virus vaccine. 140 mg glaxosmithKline/ Theravance hyperion Therapeutics Novartis/sosei Janssen Biotech Baxter/halozyme Therapeutics Pharmacyclics/Janssen Breo™ Ellipta™ (us) Ravicti™ (us) ultibro® Breezhaler® (DE.I.5 ml & 100 mg/1 ml dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates.5-ml single-dose prefilled adults to help prevent disease caused by seasonal influenza syringes (flu) virus subtypes a and type B contained in the vaccine Icosapent ethyl. or 6-mercaptopurine** glycopyrronium bromide/indacaterol*. licensed from psivida Indication Iluvien® (gB) active ingredient2 company Trade name (country)1 Table II. 190 µg*** diabetic macular edema considered insufficiently responsive to available therapies** alimera sciences. liquid solution Treatment of patients with primary humoral containing 10% Igg (100 mg/ml) for i. 50 mg/0.82 Fluticasone furoate/vilanterol*. capsules. Graul et al.v. capsules. injection supplied in 0. Wiskott-aldrich syndrome. (Cont. 50 mg/0. solution for infusion for subcutaneous immunodeficiency syndromes and in myeloma or chronic lymphocytic leukemia with severe secondary hypogammause. infusion (5 g immunodeficiency. oral liquid. This includes. X-linked agammaglobulinemia.5 ml & 100 mg/1 ml single. oral corticosteroids. quadrivalent. Nl) simponi® (us) hyQvia (DE) Imbruvica™ (us) Relief of symptoms caused by airway obstruction in patients with chronic obstructive pulmonary disease (coPD) Immune globin intravenous [human].m. 50(1) . 50 µg glycopyrronium/110 µg indacaterol. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. for administration using the Breezhaler® device chronic management of urea cycle disorders in patients 2 years of age and older long-term. 1 g amarin Vascepa™ (us) as an adjunct to diet. the in 50 ml solution & 10 g in 100 ml solution) humoral immune defect in common variable immunodeficiency (cVID). ThoMsoN REuTERs – Drugs of Today 2014. 100 µg fluticasone furoate/25 µg vilanterol glycerol phenylbutyrate. suspension for active immunization of children (3 years and older) and i. 100 mg/ml globulinemia and recurrent infections Ibrutinib. congenital agammaglobulinemia. azathioprine. but is not limited to. sterile solution in single-dose vials. nasal spray active immunization for the prevention of influenza disease in single-dose (0.active immunization for the prevention of influenza disease dose syringe.m.m. active immunization for the prevention of influenza disease caused by influenza a subtype viruses and type B viruses contained in the vaccine Indication ThoMsoN REuTERs – Drugs of Today 2014. quadrivalent. tablets. quadrivalent. 100 mg/1 mg Treatment of hypertension & 200 mg/1 mg Irbesartan/atorvastatin calcium*.50 ml single-dose vials. trivalent.5-ml doses active ingredient2 A. single-dose (2 ml) and multidose (3 ml) glass vials and 1-ml glass syringe. containing 330 mg of monobasic Treatment of hypophosphatemia** sodium phosphate monohydrate and 119 mg of dibasic sodium phosphate anhydrous Influenza virus vaccine.5-ml dose Itolizumab. prefilled pen (100 units/ml & 200 units/ml) INKP-102. ThE YEaR’s NEW DRugs & BIologIcs 2013 83 . injection. 5-ml multidose vials containing ten 0.2 ml) intranasal sprayer caused by influenza a subtype viruses and type B viruses contained in the vaccine Influenza virus vaccine. purified inactivated.0 µg per 0.25 & 0. (Cont.) New product intros – 2013.company glaxosmithKline MedImmune (astraZeneca) sanofi Pasteur Protein sciences Zeria Novo Nordisk hanmi/sanofi shionogi Kyowa hakko Kirin Biocon Bharat Biotech Trade name (country)1 Flulaval® Quadrivalent (us) FluMist® Quadrivalent (us) Fluzone® Quadrivalent (us) FluBlok® (us) Phosribbon® (JP) Tresiba® (DK) Robelito (KR) Irtra® (JP) Nouriast® (JP) alzumab™ (IN) Jenvac™ (IN) Table II.5 caused by influenza a subtype viruses and type B viruses conml for i. prefilled single. 0. suspension for i. tablets.m. granules. injection Influenza virus vaccine. 150 mg/10 mg & 150 mg/20 mg Insulin degludec. cartridge containing solution for injection (100 units/ml. vials. 0. tablets. quadrivalent. administration tained in the vaccine Influenza virus vaccine live. 5 ml containing 25 mg itolizumab Istradefylline. each containing purified inactivated Japanese encephalitis virus protein. Graul et al. 50(1) Prevention of seasonal influenza in people 18 to 49 years of age Reduction of the risk of heart disease in patients with hypertension and hyperlipidemia who are prescribed both irbesartan and atorvastatin once-daily basal insulin for the treatment of type 1 and 2 diabetes in adults Japanese encephalitis vaccine. 0. 5.I.5 ml for i. 20 mg Continued active immunization against Japanese encephalitis infection Treatment of patients with active moderate to severe chronic plaque psoriasis who are candidates for systemic therapy Improvement of wearing-off phenomena in patients with Parkinson's disease on concomitant treatment with levodopacontaining products Irbesartan/trichlormethiazide*. 10 & 20 µg glycemic control in combination with oral glucose-lowering medicinal products and/or basal insulin when these. tablets. 5. 40. 10 mg Continued Meningococcal group B vaccine [rDNa. and 0. For the treatment of adults with type 2 diabetes to achieve injection. inhalation powder. IE) alexza.) New product intros – 2013. in glass vial. apolipoprotein B (apo B) and non-hDl cholesterol in patients with familial hypercholesterolemia lorcaserin hydrochloride. component.05 mg palmitic acid. 80 & 120 mg Forest/Pierre Fabre Fetzima™ (us) Treatment of major depressive disorder in adults Indication Treatment of adults with pulmonary arterial hypertension (Who group I) to delay disease progression Macitentan. type 2 diabetes) as an adjunct to a low-fat diet and other lipid-lowering treatments. sodium salt). Graul et al. extended-release capsules. 4. intratracheal suspension. prefilled pen containing solution for s. 10 mg*** lucinactant.84 Novartis Discovery laboratories surfaxin® (us) Bexsero® (gB. 20.50 mg dipalmitoylphosphatidylcholine and 7. DE. 20.g. hypertension. prefilled syringe containing suspension for Neisseria meningitidis serogroup-B strains injection. to reduce lDl cholesterol (lDl-c). Each ml contains 30 mg phospholipids (22.c..5 ml as monotherapy or adjunctive therapy with either lithium or valproate. (Cont. total cholesterol (Tc).5 ml. including lDl apheresis where available. marketed by Ferrer adasuve® (DE) actelion arena. tablets. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. marketed and distributed by Eisai Belviq® (us) opsumit® (us) aegerion Juxtapid™ (us) sunovion sanofi. tablets. 80 & 120 mg Prevention of respiratory distress syndrome (RDs) in premature infants at high risk for RDs For rapid control of mild to moderate agitation in adult patients with schizophrenia or bipolar disorder** loxapine succinate. licensed from Zealand Pharma lyxumia® (gB) latuda® (us) levomilnacipran hydrochloride. 8. dyslipidemia.I. 0. do not provide adequate glycemic control active ingredient2 company Trade name (country)1 Table II. both to treat adult patients with major depressive episodes associated with bipolar I disorder (bipolar depression)** lurasidone hydrochloride. together with diet and exercise. 50(1) .50 mg palmitoyloleoyl-phosphatidylglycerol. ThoMsoN REuTERs – Drugs of Today 2014.862 mg sinapultide as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of • 30 kg/m2 or greater (obese) or • 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e. capsules. active immunization against invasive disease caused by adsorbed]. 40. 10 & 20 mg lixasenatide. 10 mg lomitapide. injection. single-use vials. lyophilized powder in single-use vials for reconstitution in saline. to of a 200 mg/ml solution single-use prefilled syringes treat patients with homozygous familial hypercholesIsis Pharmaceuticals containing 1 ml of a 200 mg/ml solution terolemia (hoFh) Nalmefene. meningitidis c capsular polysaccharide. single-use glass vials containing 0. licensed from Mipomersen sodium. meningitidis Y capsular polysaccharide. single-use vials containing 1 ml as an addition to lipid-lowering medications and diet. 60 mg ocriplasmin. due to menopause Paroxetine mesilate.I. 11. codeveloped by genentech and Biogen Idec Thrombogenics shionogi Noven celgene (JP) Kynamro™ (us) selincro™ (Eu) ThoMsoN REuTERs – Drugs of Today 2014.5 µg of purified Haemophilus b capsular polysaccharide glaxosmithKline Menhibrix® (us) Indication company Trade name (country)1 active ingredient2 Table II.) New product intros – 2013 A. (Cont. 5 µg purified N.5 mg Treatment of symptomatic vitreomacular adhesion in 0.25 mg genzyme. infusion shionogi.v.c.2 ml solution for intravitreal injection (2. and 2. ThE YEaR’s NEW DRugs & BIologIcs 2013 85 . Each 0. tablets. 1000 mg/40 ml for i. for the treatment of patients with previously untreated chronic lymphocytic leukemia Reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level ( > 60 g/day for men. 18 mg obinutuzumab. Graul et al. 7. > 40 g/day for women) without physical withdrawal symptoms and who do not require immediate detoxification** Treatment of congenital lipodystrophy active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups c and Y and Haemophilus influenzae type b in children 6 weeks of age through 18 months of age Meningococcal groups c and Y and Haemophilus b tetanus toxoid conjugate vaccine. capsules. 4 mg Continued Treatment of moderate to severe vasomotor symptoms associated with menopause** Treatment of moderate to severe dyspareunia.5 mg ospemifene.Metreleptin. licensed from amylin BioTie Therapies/lundbeck Roche. a symptom of vulvar and vaginal atrophy.5-ml dose contains 5 µg purified N.5 mg/ml) In combination with chlorambucil. 50(1) gazyva™ (us) Jetrea® (us) osphena™ (us) Brisdelle™ (us) Pomalyst® (us) Treatment of multiple myeloma in patients who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy Pomalidomide. film-coated tablets. vials for s. capsules. powder for reconstitution.) New product intros – 2013. 45 mg ariad Pharmaceuticals Iclusig™ (us) Treatment of advanced stage non-small cell lung cancer in patients undergoing chemotherapy and radiotherapy treatment or in patients who have not responded to first-line therapy Treatment of adult patients with chronic.I. ThoMsoN REuTERs – Drugs of Today 2014. 1. 5 g sBI/packet Continued Treatment of hypertriglyceridemia in type 2 diabetic patients not controlled by statins alone For the management of inoperable chronic thromboembolic pulmonary hypertension (cTEPh. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. 1.. single-use vials at a con. diarrhea-predominant irritable bowel syndrome [IBs-D]) and in patients with chronic loose or frequent stools who are infected with hIV serum-derived bovine immunoglobulin/protein isolate (sBI). because of therapeutic or chronic medical needs.v. 50(1) . tablets. infusion Radium Ra 223 dichloride.Treatment of patients with castration-resistant prostate centration of 1. accelerated or blast phase chronic myeloid leukemia (cMl) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ all) that is resistant or intolerant to prior TKI therapy**** Indication clinical dietary management of enteropathy under medical supervision for patients who. vials.5 mg Raxibacumab. or who have chronic loose or frequent stools (e.5. 0.g.5. Graul et al. developed and marketed by Bayer schering Pharma Xofigo® (us) Zydus Recombio Vaxira® (aR) lipaglyn™ (IN) Ponatinib. have limited or impaired capacity to ingest. 4 mg Riociguat.0 & 2. digest. absorb or metabolize ordinary foodstuffs or certain nutrients. (Cont. 2. tablets. Who group 4) and of persistent or recurrent cTEPh after surgical treatment in adult patients (≥ 18 years of age) with Who functional class II or III pulmonary hypertension Treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate saroglitazar.86 Bayer adempas® (ca) Entera health glaxosmithKline (us) Enteragam™ (us) algeta. single-use vials containing 1700 mg/34 ml (50 mg/ml) solution for i.000 kBq/ml (27 microcurie/ml) at the cancer. film-coated tablets. 1 ml containing 1 mg racotumumab for intradermal injection active ingredient2 company Trade name (country)1 Table II.000 metastatic disease kBq/vial (162 microcurie/vial) at the reference date Racotumomab.0. symptomatic bone metastases and no known visceral reference date with a total radioactivity of 6. and vial containing sodium phosphate injection 355 mg/25 ml.c.16 mg/ml) vincristine sulfate Technetium Tc 99m tilmanocept. usP 5 mg/5 ml. and Treatment for adult patients with short bowel syndrome solvent. increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia (BPh) in men who are not adequately responding to treatment with monotherapy Treatment of adult patients with Philadelphia chromosome negative (Ph–) acute lymphoblastic leukemia (all) in second or greater relapse or whose disease has progressed following two or more antileukemia therapies Treatment of chronic hepatitis c virus infection as a component of a combination antiviral treatment regimen For use in combination with pegylated interferon (PEg-IFN) and ribavirin for the treatment of genotype 1 chronic hepatitis c virus (hcV) patients who are treatment-naive. 400 mg gilead sovriad® (JP) sovaldi™ (us) Continued Indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma Treatment of moderate to severe storage symptoms (urgency. (Cont. 103 mg/ml. A. 100 mg (JP) and capsules.5 mci) and 250 µg of technetium Tc 99m tilmanocept in 0. modified-release tablet. capsules. injection spectrum Pharmaceuticals astellas Navidea Biopharmaceuticals.ThoMsoN REuTERs – Drugs of Today 2014. vial containing sphingomyelin/cholesterol liposome injection.4 mg tamsulosin/6 mg solifenacin sofosbuvir.5 ml to 5 ml total volume. 150 mg (us) Janssen licensed from Medivir Indication olysio™ (us) active ingredient2 company Trade name (country)1 Table II.5 MBq (2. prior nonresponders or relapsed following treatment with PEg-IFN with or without ribavirin simeprevir. kit consisting of vial containing vincristine sulfate injection.5 ml in prefilled syringe. sold and distributed by cardinal health NPs Pharmaceuticals Marqibo® (us) Vesomni™ (Nl) lymphoseek® (us) gattex® (us) Tamsulosin hydrochloride/solifenacin succinate*. intradermal or peritumoral injection Teduglutide [rDNa origin]. each single-use vial of Marqibo contains 5 mg/31 ml (0. Graul et al. after preparation. powder in vials. kit for preparation of lymphoseek containing five tilmanocept powder vials each containing 250 µg tilmanocept and five Diluent for lymphoseek vials containing 4. tablets. 5 mg. 0. lymphoseek contains approximately 92. for reconstitution (5 mg/0. 0.5 ml) and s. 50(1) sphingosomal vincristine.5 ml of sterile buffered saline. ThE YEaR’s NEW DRugs & BIologIcs 2013 87 .) New product intros – 2013. after radiolabeling with technetium Tc 99m and dilution.I. For subcutaneous. 40 & 60 mg Kenkyusho/Fuji Yakuhin uriadec® (JP) Topiloric® (JP) active ingredient2 company Trade name (country)1 Table II. ***New formulation. prefilled syringes. *New combination.I. ****Marketing temporarily suspended. ThE YEaR’s NEW DRugs & BIologIcs 2013 A. 20. tablets. lyophilized powder in single. 1 Typhoid conjugate vaccine.88 Vortioxetine.as a single agent. ThoMsoN REuTERs – Drugs of Today 2014. tablets.5. Patients should have either received prior therapy for metastatic disease. licensed from Japan Tobacco Mekinist™ (us) Trametinib dimethyl sulfoxide. **New indication. are ordered alphabetically by active ingredient. 5. 0. 1 & 2 mg sanwa Kagaku Topiroxostat. (Cont.) New product intros – 2013. separately or in combination. tablets. Graul et al. 25 µg/dose in 0. 50(1) . codeveloped and comarketed by Takeda Kadcyla™ (us) Typbar-TcV™ (IN) Brintellix™ (us) 2Products Treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E and V600K mutations as detected by an FDa-approved test Treatment of gout and hyperuricemia Indication Treatment of major depressive disorder in adults Prevention of typhoid disease in adults and infants aged > 6 months to 45 years Trastuzumab emtansine. for the treatment of patients with hER2positive. or developed disease recurrence during or within 6 months of completing adjuvant therapy country codes are the abbreviations used by the World Intellectual Property organization.5 ml glaxosmithKline. metastatic breast cancer who previously received use vials containing 100 mg/vial or 160 mg/vial trastuzumab and a taxane. 10 & 20 mg Roche Bharat Biotech lundbeck. Graul et al.A.HCl CH3 acotiamide hydrochloride hydrate F CH3 N Br N H3C O N CH3 HO O O Bedaquiline N afatinib H N H N O O H3C Cl N O CH3 H3C HN HN CH3 O O . 50(1) F H N O F N N canagliflozin F S O F .I.CH3SO3H NH2 Dabrafenib mesilate 89 . ThE YEaR’s NEW DRugs & BIologIcs 2013 Chemical structures of NCEs launched in 2013 O H3C H3C S O N H O CH3 H N N O OH N H3C 3. HO F O OH O OH N O cabozantinib S-malate H3C CH3 O HO HO CH3 N H3C S S OH OH ThoMsoN REuTERs – Drugs of Today 2014.H2O CH3 . New launches .ThE YEaR’s NEW DRugs & BIologIcs 2013 A. Graul et al.I.HCl N CH3 F CH3 levomilnacipran hydrochloride F F F O O N NH N H lomitapide 90 ThoMsoN REuTERs – Drugs of Today 2014.structure list for TYND 2013 CH3 O H3C O OH O F O N H N O O F N H O Dimethyl fumarate CH3 O Dolutegravir O O O O O O O NH2 glycerol phenylbutyrate N N N O H3C N O CH3 O N N O N CH3 N N CH3 CH2 O H3C Ibrutinib Istradefylline NH2 F O F . 50(1) . HCl Cl N H3C lorcaserin hydrochloride O O O N OH ospemifene NH O NH2 O Pomalidomide F N N N CH3 H3C N H2N NH2 H3C Br Macitentan Cl N N O O N N O CH3 O Riociguat ThoMsoN REuTERs – Drugs of Today 2014.A. ThE YEaR’s NEW DRugs & BIologIcs 2013 New launches . Graul et al.I.structure list for TYND 2013 O H3C N H O S Br NH N NH . 50(1) H N N N O N N F F F N Ponatinib 91 . 50(1) .HBr N H Vortioxetine hydrobromido ThoMsoN REuTERs – Drugs of Today 2014. Graul et al.structure list for TYND 2013 CH3 O CH3 H3C S CH3 N N O O N CH3 S O CH3 OH CH3 O H N O O O N H3C saroglitazar O S N H O simeprevir O HN O O CH3 H3C O CH3 HO N N F Topiroxostat I F HN N O N N CH3 CH3 O .I.ThE YEaR’s NEW DRugs & BIologIcs 2013 A. O H3C CH3 O N H CH3 Trametinib dimethyl sulfoxide 92 CN CH3 sofosbuvir O N N O P O N H O O H N N S S CH3 N CH3 . New launches . company ucB Biocon sanofi/Zealand Pharma Takeda Janssen Therapeutics Product name (trade name) certolizumab pegol (cimzia) Itolizumab (alzumab) lixasenatide (lyxumia) ThoMsoN REuTERs – Drugs of Today 2014.057 32.123 32.311 35.024 41. ThE YEaR’s NEW DRugs & BIologIcs 2013 93 . usD) Table III.I.293 - 387 - 1. 29. usD) A.956 lantus Degludec/Tresiba Invokana Tenelia Nesina onglyza/Kombiglyze galvus/Eucreas glucophage/Metgluco Victoza humulin Januvia/glactiv Welchol Novolog/NovoRapid/Novo mix Basen actos Tradjenta/Trajenta Janumet Forxiga NovoNorm/Prandin/Prandi Met/NovoMet/ surepost glumetza cycloset liovel amaryl Byetta Fastic/starsis glufast Bydureon glucobay Juvicor/Xelezor Diastobol humira Neoral/sandimmune Diprolene/ Rinderon Enbrel Remicade Fumaderm allelock Elocon/Fulmeta centocor Tazorac/Zorac humira/humira Pen Remicade stelara simponi Enbrel lodotra cimzia Drug's estimated competitors’ trade sales 2018 names (million. 50(1) alogliptin benzoate/metformin hydrochloride (Kazano) canagliflozin (Invokana) Treatment of with type 2 diabetes Treatment of plaque psoriasis Treatment of active psoriatic arthritis Indication 1.932 30.013 competitors' competitors' estimated sales 2013 estimated sales 2018 (million.316 31. Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. Graul et al.790 Continued 40. usD) (million. 701 20. Graul et al. usD) ThE YEaR’s NEW DRugs & BIologIcs 2013 A. usD) Table III. 17.032 28.614 Continued 15.256 12.573 Isentress Edurant Trizivir Reyataz Viread Prezista complera/Eviplera stribild Truvada crixivan/strocin Intelence Kaletra Fuzeon Zerit/Zerit XR Norvir Emtriva atripla combivir Viracept selzentry Epivir lexiva Telzir agenerase Epzicom/Kivexa Videx Zestril cleviprex olmetec/Benitec/Benicar Micardis atacand/Parapres Diovan/co-Diovan unisia azilva coreg IR/coreg cR calblock caduet cardura Norvasc/amlodin concor Tanatril Bystolic aimix aprovel/av alide Inspra Detantol Tenormin coniel Exforge luprac cozaar/hyzaar seloken/Toprol Xl Tritace Vasotec/Vaseretic Tekturna Monopril Tribenzor/sevikar hcT lotrel azor/sevikar acequin - - Delzicol humira Prograf Remicade asacol Budenofalk ultesa/uceris/cortiment Pentasa salofalk lialda/Mezavant colazal 2.208 23.100 competitors' competitors' estimated sales 2013 estimated sales 2018 (million. ThoMsoN REuTERs – Drugs of Today 2014. 50(1) .) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. (Cont. usD) (million.945 Drug's estimated competitors’ trade names sales 2018 (million.I.94 ViiV healthcare Dolutegravir (Tivicay) hanmi/sanofi Irbesartan/ atorvastatin calcium (Robelito) shionogi Janssen Biotech golimumab (simponi) Irbesartan/ trichlormethiazide (Irtra) company Product name (trade name) Treatment of hIV-1 infection Treatment of hypertension Reduction of the risk of heart disease in patients with hypertension and hyperlipidemia Treatment of ulcerative colitis Indication 1. Merck & co. ThE YEaR’s NEW DRugs & BIologIcs 2013 95 . usD) (million.757 13. A.I.967 12.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. usD) lipitor Welchol livazo Zocor Zetia Kynamro crestor Vytorin Niaspan Mevacor lescol argatrovan lipitor crestor Radicut Xarelto Novastan Fragmin arixtra coumadin lovenox angiomax Fraxiparine axanum gilenya copaxone Tysabri Fampyra/ampyra avonex aubagio Betaferon Rebif Extavia alvesco symbicort Turbuhaler Relovair Xopenex lodotra Flutiform Pulmicort Dulera Foradil seretide/ advair Ventolin serevent Prozac cipralex/Emtact/lexapro Zoloft cymbalta Effexor/Effexor XR Pristiq abilify seroxat/Paxil Viibryd Wellbrutin Xl/Zyban Remeron Drug's estimated competitors’ trade names sales 2018 (million.335 competitors' competitors' estimated sales 2013 estimated sales 2018 (million.850 17.318 5.293 15. usD) Table III. tatin (liptruzet) Biogen Idec Dimethyl fumarate (Tecfidera) glycopyrronium Novartis/sosei bromide/indacaterol (ultibro Breezhaler) company Product name (trade name) 1. (Cont.085 18 2.007 870 2.265 Continued 15.611 humulin Novolog/NovoRapid/ Novomix lantus 14.369 5.776 4.950 15.ThoMsoN REuTERs – Drugs of Today 2014. 50(1) Forest/Pierre Fabre lundbeck/Takeda glaxosmithKline/ Theravance levomilnacipran hydrochloride (Fetzima) Vortioxetine (Brintellix) Fluticasone furoate/vilanterol (Breo Ellipta) Treatment of type 1 and 2 diabetes in adults Novo Nordisk Insulin degludec (Tresiba) Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation Treatment of primary or mixed hyperlipidemia and homozygous familial hypercholesterolemia (hoFh) Bristol-Myers squibb/Pfizer apixaban (Eliquis) Treatment of patients with relapsing forms of multiple sclerosis Treatment of chronic obstructive pulmonary disease (coPD) Treatment of major depressive disorder Indication Ezetimibe/atorvas.412 10.342 26. Graul et al.219 - 274 14. 50(1) .822 6.059 8. usD) Treatment of advanced stage non-small cell lung cancer (Nsclc) Treatment of homozygous familial hypercholesterolemia (hoFh) Indication Treatment of chronic myeloid leukemia (cMl) or Ph+ acute lymphoblastic leukemia (Ph+ all) ariad Pharmaceuticals aegerion lomitapide (Juxtapid) Ponatinib (Iclusig) company Product name (trade name) Table III. 5.161 8.473 - Treatment of major depressive episodes associated with bipolar I disorder (bipolar depression) Treatment of multiple myeloma - 175 748 Eylea lucentis Macugen sprycel gleevec/glivec Erwinaze/Erwinase clolar/ Evoltra Tasigna sprycel gleevec/glivec adcirca Revatio adempas Tracleer letairis Ventavis Remodulin Veletri Tyvaso Kyprolis Treanda Velcade Thalomid Revlimid sumiferon Doxil/caely seroquel IR/XR Zyprexa abilify Tegretol carbatrol lamictal geodon Taxol gemzar avastin abraxane Tarceva Xalkori Taxotere Paraplatin Iressa lojuxta lipitor Zetia Kynamro crestor Vytorin lescol/lochol Drug's estimated competitors’ trade names sales 2018 (million.064 7. (Cont. Graul et al. usD) ThE YEaR’s NEW DRugs & BIologIcs 2013 A.I.336 9.96 genzyme/Isis Pharmaceuticals Recombio sunovion celgene actelion Bayer Mipomersen sodium (Kynamro) Racotumomab (Vaxira) lurasidone hydrochloride (latuda) Pomalidomide (Pomalyst) Macitentan (opsumit) Riociguat (adempas) - Treatment of symptomatic vitreomacular adhesion ocriplasmin (Jetrea) Thrombogenics - Treatment of Ph– acute lymphoblastic leukemia (all) sphingosomal vin.696 13.754 10.931 competitors' estimated sales 2018 (million.159 241 Management of chronic thromboembolic pulmonary hypertension Treatment of pulmonary arterial hypertension 1.633 2. usD) Continued 9.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013.248 5. ThoMsoN REuTERs – Drugs of Today 2014.300 5.391 competitors' estimated sales 2013 (million.spectrum cristine (Marqibo) Pharmaceuticals 488 1.818 10.728 13.160 3.393 5. usD) A.062 1.968 2. 1.860 3. olysio) afatinib (giotrif) ThoMsoN REuTERs – Drugs of Today 2014. usD) (million.484 3.917 competitors' competitors' estimated sales 2013 estimated sales 2018 (million.548 1.Treatment of hER2-positive metastatic breast cancer Roche gilead Janssen/Medivir Boehringer Ingelheim Trastuzumab emtansine (Kadcyla) sofosbuvir (sovaldi) simeprevir (sovriad.I.455 Continued 855 - 998 1.826 Drug's estimated competitors’ trade names sales 2018 (million.275 2.987 4.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. 50(1) Ibrutinib (Imbruvica) - amarin Zydus Biotest Pharmaceuticals Mitsubishi Tanabe Treatment of hyperphosphaPharma/NextPharma temia in chronic kidney disease Icosapent ethyl (Vascepa) saroglitazar (lipaglyn) Immune globin intravenous [human] (Bivigam) colestilan (BindRen) Treatment of primary humoral immunodeficiency Treatment of hypertriglyceridemia - 443 Fosrenol Renvela/Renagel gammagard Niaspan Mevalotin Mecavor atozet Juvicor/Xelezor/Tesozor lovaza Vascepal/Miraxion Neupro Trerief Madopar azilect Permax stalevo/comtess/comtan Requip sinemet apokyn - Kyowa hakko Kirin Istradefylline (Nouriast) Improvement of wearing-off phenomena in patients with Parkinson's disease coagulation factor IX deficiency (hemophilia B) Baxter coagulation factor IX (recombinant) (Rixubis) Treanda Velcade Torisel BeneFIX Novoseven 3. Graul et al.635 1. usD) Treatment of metastatic nonsmall cell lung cancer (Nsclc) Treatment of hepatitis c virus infection Indication company Product name (trade name) Table III.506 3. ThE YEaR’s NEW DRugs & BIologIcs 2013 97 .677 Treatment of patients with mantle cell lymphoma Pharmacyclics/ Janssen Xalkori gemzar alimta Iressa Incivek Rebetol olysio Pegasys Victrelis uRso copegus sumiferon PegIntron Taxol gemzar afinitor/certican abraxane halaven Taxotere Tykerb Ixempra Faslodex arimidex 29 - 260 6. (Cont.259 4.571 2.813 7.762 2.417 1. usD) (million.180 1.294 1. ThoMsoN REuTERs – Drugs of Today 2014.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013.109 1. component. usD) ThE YEaR’s NEW DRugs & BIologIcs 2013 A. quadrivalent (Flulaval) Influenza virus sanofi Pasteur vaccine. adsorbed] (Bexsero) glaxosmithKline Toa Eiyo/astellas Pharma Meningococcal groups c and Y and haemophilus b tetanus toxoid conjugate vaccine (Menhibrix) Bisoprolol (Bisono Tape) Treatment of essential hypertension Treatment of active systemic juvenile idiopathic arthritis (sJIa) and gouty arthritis Novartis canakinumab (Ilaris) - 260 800 377 - Influenza virus vaccine (FluBlok) Influenza virus glaxosmithKline vaccine. usD) - Prevention of influenza (a and B) Indication Protein sciences Influenza virus MedImmune vaccine live (FluMist (astraZeneca) Quadrivalent) Product name (trade name) Table III. quadrivalent (Fluarix) 300 herbesser Plendil adalat Verelan Merrem/Meropen ocephin Menveo ceftin/Zinacef uloric colcrys arcoxia Rapiacta/PeramiFlu Tamiflu Fluvirin Fluviral Relenza Drug's estimated competitors’ trade names sales 2018 (million.168 912 competitors' competitors' estimated sales 2013 estimated sales 2018 (million. 50(1) .214 1.092 912 Continued 1. (cont. 1.98 company - - Influenza virus glaxosmithKline vaccine. Graul et al.I. quadrivalent (Fluzone) active immunization against invasive disease caused by Neisseria meningitidis serogroup-B strains active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups c and Y and Haemophilus influenzae type b Meningococcal Novartis group B vaccine [rDNa. Topiloric) lorcaserin hydrochloride (Belviq) Brinzolamide/ brimonidine tartrate (simbrinza) anakinra (Kineret) Treatment of neonatal-onset multisystem inflammatory disease (NoMID) Reduction of intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension Weight management Treatment of cataplexy in patients with narcolepsy glaxosmithKline Raxibacumab (abthrax) Treatment of inhalational anthrax due to Bacillus anthracis glaxosmithKline Dabrafenib mesilate (Tafinlar) Treatment of BRAF-mutated metastatic melanoma Trametinib dimethyl glaxosmithKline/ sulfoxide (Mekinist) Japan Tobacco Indication Treatment of moderate to severe vasomotor symptoms associated with menopause company Noven Paroxetine mesilate (Brisdelle) Product name (trade name) - - 436 - 582 - - - - 502 666 - 167 115 Ilaris 376 336 775 Continued 258 262 182 313 206 1.178 962 835 965 competitors' estimated sales 2018 (million. usD) Tapros Rescula Xenical Qsymia uloric saizen / serostim allelock Fulmeta activella Estrace Xyrem levaquin/Floxin ozex Doryx cipro/ciprobay Yervoy Premarin Drug's estimated competitors’ trade names sales 2018 (million.I.289 317 406 565 567 553 2. usD) 1.063 competitors' estimated sales 2013 (million. A.ThoMsoN REuTERs – Drugs of Today 2014. (Cont. 50(1) Treatment of moderate to severe dyspareunia due to menopause Topical treatment of persistent facial erythema of rosacea Treatment of short bowel syndrome alfresa Pharma shionogi galderma NPs Pharmaceuticals sanwa Kagaku Treatment of gout and Kenkyusho/Fuji Yakuhin hyperuricemia arena/Eisai alcon (Novartis) swedish orphan BioVitrum clomipramine hydrochloride (anafranil) ospemifene (osphena) Brimonidine tartrate (Mirvaso) Teduglutide (gattex) Topiroxostat (uriadec. usD) Table III.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. Graul et al. ThE YEaR’s NEW DRugs & BIologIcs 2013 99 . usD) (million.) Estimated market size for selected new drugs and biologics and new line extensions launched in 2013. metastatic medullary thyroid cancer cabozantinib Exelixis S-malate (cometriq) Reduction of alcohol consumption in adult patients with alcohol dependence Treatment of moderate to severe storage symptoms (urgency. (Cont. increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia BioTie Therapies/ lundbeck Nalmefene (selincro) Indication Tamsulosin astellas hydrochloride/ solifenacin succinate (Vesomni) company Product name (trade name) Table III. ThoMsoN REuTERs – Drugs of Today 2014. Graul et al.hyperion tyrate (Ravicti) Therapeutics Zeria/astellas Pharma acotiamide hydrochloride hydrate (acofide) collagenase auxilium Clostridium histolyticum (Xiaflex) Treatment of giant cell tumor of bone amgen Denosumab (Xgeva) Treatment of patients with previously untreated chronic lymphocytic leukemia Treatment of progressive. - - - - - - - 49 73 82 - - - - - - - 156 23 361 competitors' competitors' estimated sales 2013 estimated sales 2018 (million. usD) glycerol phenylbu.189 3. December 2013.100 Roche/genentech/ Biogen Idec algeta/Bayer schering Pharma obinutuzumab (gazyva) Radium Ra 223 dichloride (Xofigo) 68 symptomatic relief of noninfectious diarrhea in adult patients with hIV/aIDs on antiretroviral therapy crofelemer (Fulyzaq) source: Thomson Reuters cortellisTM and Thomson Reuters IntegritysM. salix/Napo 136 140 Treatment of congenital lipodystrophy chronic management of urea cycle disorders shionogi licensed from amylin Metreleptin (leptin) 243 280 937 Treatment of functional dyspepsia Treatment of Peyronie's disease Treatment of patients with castration-resistant prostate cancer with symptomatic bone metastases 1.803 301 - 350 - - - - - - - caprelsa Enablex selincro campral Drug's estimated competitors’ trade names sales 2018 (million. usD) ThE YEaR’s NEW DRugs & BIologIcs 2013 A.I. 50(1) .