MM&M takes a detailed look at key products in the pipeline, highlighting the most promising with insights and ratings from Ptop analysts, to IPE provide an overall picture of each therapeutic’s potential value INE 2010 uerosto commodo odionul PROVOCATIVE

AGMM&M’s Pipeline 2010 drawsENTS from the best in drug development, profiling 15 agents with the highest approval probability and brightest commercial prospects. These are the prime near-term launch candidates. The report also provides updates on 202 products in a host of therapeutic areas. Marc Iskowitz reports

ualitative change, rather than the quantitative kind, marks best hope to replace warfarin. Then there are the upstarts. Patients this year’s biopharmaceutical pipeline. There has been a shift with rare diseases are finally getting drugs specifically approved for Q in categories poised to yield near-term approvals. And while them. According to a new analysis by the Tufts Center for the Study not the goldmine drug marketers were hoping for, analysts expect of Drug Development, the annual rate of new product approvals the 2010 R&D seam to yield some exciting launch prospects in the worldwide for neglected diseases increased from an average of 1.8 months and years ahead. in 1975-99 to 2.6 in 2000-09. Vaccines and antiviral drugs have also Oncology, a well of innovative approvals in years past, has run seen a resurgence, with physicians talking about a possible cure for relatively dry. “In 2000-2001, we saw Avastin, Tarceva, Sutent, Nexa- hepatitis C and a number of vaccines in the pipeline for ailments var, Gleevec—drugs that revolutionized the way we think about from flu to and diabetes. treating cancer,” notes Ben Weintraub, PhD, director of research, These drug-development dynamics are borne out in MM&M’s Wolters Kluwer inThought. “The second half of this decade is about Pipeline 2010. The report captures the latest trends, profiling 15 using them properly.” agents with a high probability of reaching market and bright com- Another category making less noise is neurology, with scientists’ mercial prospects. Surveying today’s drug-development scene, the search for an effective Alzheimer’s disease treatment one of the report highlights the rare disease and infectious disease categories, lone highlights. In , oral therapy (Merck/ along with stalwarts cardiovascular, metabolic and rheumatology. A Serono) is set to enter a self-injection and infusion market. Yet ana- final category keeps readers updated on neurology, women’s health, lysts see few potential game-changers among Parkinson’s disease, respiratory and oncology product candidates. schizophrenia, depression or pain candidates. The top picks are based on Wolters Kluwer data. Each profiled drug includes a percentage called the inThought Approvability A cardiovascular blockbuster? Index (IAI)—anything above 50% has a good chance—and, where The cardiovascular pipeline, on the other hand, contains a slew of available, a revenue forcecast. The IAI uses historical approval rates provocative agents that could make a big impact. Indeed, the next and detailed analysis of clinical trials to model the probability of blockbuster may be a clot-buster, with Johnson & Johnson and Bay- approval. Each featured section of the pipeline also includes a box er’s Xarelto (rivaroxaban) anticoagulant shaping up to be physicians’ containing additional key products (from Wolters Kluwer data).

Therapeutic Categories: Cardiovascular 43 Metabolic 45 Rheumatology 47 Infectious Disease 44 Rare Diseases 46 Others 48

42 MM&M x DECEMBER 2009 x mmm-online.com PIPELINE 2010 Cardiovascular PRODUCTS GENERATING BUZZ OTHER KEY PRODUCTS IN THE PIPELINE Xarelto (rivaroxaban) Johnson & Johnson/Bayer Indication: VTE (Prereg.); ACS, stroke prevention (Ph. III) What the clinical trials found: All four RECORD studies have shown ABT 335/Crestor Combination Binodenoson King Abbott/AstraZeneca Cardiovascular disorders (Prereg.) rivaroxaban reduces deep vein thrombosis and pulmonary embolism (Ph. III) compared with enoxaparin (Lovenox), with similarly low bleeding rates. Acadesine Merck Xience V (Bio-Absorbable) Ischem. heart disease. (Ph. III) Revenue forecast: $6.8 billion worldwide by 2015, says Craig Max- well of ING Financial Markets Stent (Ph. III) Anacetrapib Merck Atherosclerosis (Ph. III) inThought Approvability Index and Comment: 95% (VTE), 53% Clonidine Addrenex (stroke prevention in AFib). Physicians have been hoping for an Hypertension (Prereg.) Cordaptive Merck oral anticoagulant to replace Coumadin (warfarin) for decades. The Atherosclerosis (Ph. III) Lomitapide Aegerion implosion of AstraZeneca’s factor Xa inhibitor Exanta a few years Hyperlipoproteinemia type II (Ph. III) MK-0524B Merck ago because of safety concerns has left the FDA cautious about Hyperlipidemia (Ph. III); Atherosclerosis Bucindolol ARCA (Ph. III) approving such agents, but inThought believes that rivaroxaban has Heart failure (Prereg.) a good benefit-risk profile and will be well-accepted by physicians. SCH 530348 Merck Tecerfarin ARYx ACS (Ph. III) The drug, already approved in Europe, will be approved in the US Thromboembolism (Ph. II/III) first for prophylaxis among patients with venous thromboembo- Colestilan Mitsubishi lism (VTE). It also has potential in stroke prevention in patients YM150 Astellas Hyperphosphatemia (Ph. III) Venous thrombosis. (Ph. II/III) with atrial fibrillation (AFib) and various other clinical scenarios. Rolofylline NovaCardia (Merck) Estimated approval for VTE in the US: April 2010 (Source: Wolters Sematilide Bayer Acute heart failure (Ph. III) Arrhythmias (Ph. III) Kluwer Health). rFXIII Novo Nordisk What the analysts had to say: Physicians are looking for a more -based therapies Bioheart Factor XIII defiency (Ph. III) Heart dam. (Ph. III) convenient and efficacious alternative to warfarin without increased Azimilide P&G bleed risk. Xarelto, as well as Pradaxa (dabigatran), will meet some of Apixaban BMS/ AF, atrial flutter., supraventricular these needs. Both are once-daily, oral and don’t require coagulation ACS, DVT, stroke (Ph. III) arrhythmias (Prereg.), arrhythmias, post-MI (Ph. III) monitoring, but Xarelto lags Pradaxa for stroke. The FDA’s request Kynapid (vernakalant) for data on Xarelto’s VTE application is slowing development. Cardiome/Merck/Astellas Desmoteplase PAION AF acute (Ph. III); maintenance (Ph. II) Stroke (Ph. III) —Mary McBride, Associate VP, GfK Healthcare Alferminogene Cardium MPC 028 URL Pharma Myocardia ischem. (Ph. III) Hyper-cholesterolemia, -lipidemia, Pradaxa (dabigatran) Boehringer Ingelheim -triglyceridemia (Prereg.) Indication: VTE, stroke prevention (Ph. III) TRIA 662 Cortia Hyperlipidemia (Ph. II/III) AVE 5026 Sanofi-Aventis What the clinical trials found: The RE-LY 18,113-patient phase Thromboembolism (Ph. III) III trial showed subjects randomized to 150 mg of dabigatran twice DOV a day had significantly lower rates of both hemorrhagic stroke and Angina, hypertension (Ph. III) AVE 5530 Sanofi-Aventis Hypercholesterolema (Ph. III) ischemic stroke than patients taking warfarin. Defibrotide Gentium inThought Approvability Index and Comment: 67%. Like rivar- Veno-occlusive disease. (Ph. III) Idrabiotaparinux Sanofi-Aventis Embolism (Ph. III) oxaban, this oral anticoagulant is exciting because of its potential to Mipomersen Genzyme replace warfarin. Dabigatran’s best evidence is for use in patients Hyper-cholesterolaemia, -lipoproteine- Terutroban Servier with atrial fibrillation at risk for stroke, where experts predict it mia type IIa (Ph. III) Cardiovascular disease (Ph. III) could capture 50% of warfarin’s market within five years of approval Gilead Azilsartan Takeda (Source: Wolters Kluwer Health). Resistant hypertension (Ph. III) Hypertension (Ph. III) What the analysts had to say: This oral direct thrombin inhibitor Darapladib GlaxoSmithKline Xemilofiban VDDI is well ahead of agents across classes and should be well-received by Atherosclerosis (Ph. III) Cardiovascular disease (Ph. III) physicians for stroke prevention. The RE-LY trial showed promising GlaxoSmithKline results, with comparable efficacy to warfarin without increased bleed Hypereosinophilic syndrome (Ph. III) risk or . Rapid onset of action and lack of coagulation monitoring suggest both physicians and patients will welcome this easier-to-use warfarin alternative. —Mary McBride, Associate VP, GfK Healthcare

mmm-online.com x DECEMBER 2009 x MM&M 43 uerosto commodo odionul Infectious Disease PRODUCTS GENERATING BUZZ OTHER KEY PRODUCTS IN THE PIPELINE Telaprevir Vertex/Johnson & Johnson Indication: Hepatitis C (Ph. III) What the clinical trials found: Phase II results showed excellent Japanese encephalitis vaccine Gardasil (women 27-45) Merck Acambis HPV vaccine (Reg. / Filed) antiviral activity, offering improved efficacy and reduced duration Japanese encephalitis (Ph. III) of treatment vs. conventional therapy. Vicriviroc Merck Sorivudine topical aRigen HIV-1 infection (Ph. III) inThought Revenue forecast: $1.9 billion US, $2.9 billion world- Herpes zoster (Ph. II/III) wide, by 2016 V503 (vaccine) Merck Apricitabine Avexa HPV infection (Ph. III); Cervical, vul- inThought Approvability Index and Comment: 81%. One of the HIV-1 infection (Ph. III) vovaginal cancer (prev.) (Ph. III) most exciting drugs in development, telaprevir has been generating DR 5001 Barr Meningococcal vaccine groups exciting results in patients with hepatitis C, with some physicians Adenovirus infection (Ph. III) ACY W-135 conj. Novartis actually talking about a cure. If approved, this drug would be used Meningococcal group A, C, Y, W-135 in combination with and ribavirin. The most notable Seasonal influenza virus vaccine infection (Prereg.) Baxter adversity to date is a sometimes severe rash. Estimated approval: Seasonal flu (Ph. III) Tifacogin Novartis January 2012 (Source: Wolters Kluwer Health). CAP (Ph. III) B cell vaccine What the analysts had to say: Telaprevir, as well as boceprevir (see Biovest/NCI West Nile immune globulin OMRIX below), represent new entries in the class referred to as “STAT-Cs,” NHL (Ph. III) West Nile virus infection (Ph. III) or specifically targeted anti-virals for the treatment of hepatitis C. Sipuleucel-T (vaccine) Dendreon Cancer vaccine BLP25 Oncothy- Physicians are strongly anticipating both. The two are approximately Prostate (ref.) (Prereg.) reon/Merck KGaA comparable from the standpoint of sustained virologic response in , NSCL (Ph. III) Heplisav (hep. B vaccine) Dynavax genotype 1 patients. Telaprevir also offers the benefit of a potentially HBV infection (Ph. III) Fidaxomicin/OPT80 Optimer shortened duration of therapy for genotype 1 patients—24 weeks Clostridium infections (Ph. III) Eritoran Eisai vs. 48. —Noah Pines, EVP, GfK Healthcare Gram-neg. infection, septic shock Pneumococcal vaccine conjugate (Ph. III) 13-valent Pfizer Boceprevir Merck Pneumococcal infection (Prereg.), PRO 2000 Endo elderly (Ph. III) Indication: Hepatitis C (Ph. III) HIV infection (Ph. III) What the clinical trials found: The phase II HCV SPRINT-1 trial Zithromax/ Chloroquine Pfizer Elvitegravir Gilead/Japan Tobacco Malaria (Ph. III) showed that in treatment-naïve patients with HCV genotype 1 HIV-1 infection (Ph. III) infection, a 48-week regimen that included boceprevir 800 mg twice Influenza virus vaccine GSK 1572932A GlaxoSmithKline daily resulted in a sustained virological response rate of 75% at Sciences NSCL (Ph. III) Influenza virus infection (Prereg.) 24 weeks, compared with 38% in the control group who received Inactivated split-trivalent seasonal peginterferon alfa-2b + ribavirin alone. Mycophenolate mofetil Roche flu vaccine GlaxoSmithKline Pemphigus vulgaris (Ph. III) inThought Revenue forecast: $345 million US, $775 million world- Seasonal flu (Elderly) (Ph. III) wide, by 2016 Crofelemer Salix Hib-meningococcal vaccine groups Diarrhea (Ph. III) inThought Approvability Index and Comment: 71%. Unfortu- C and Y conj. GlaxoSmithKline nately for Merck, boceprevir’s profile doesn’t appear as exciting Haemophilus infection (Ph. III); Meningo- Influenza virus vaccine High Dose as telaprevir’s, with slower viral clearance and 50% of patients coccal groups C & Y infection (Ph. III) Sanofi Pasteur Influenza virus infection elderly experiencing anemia. Still, it could become an important new agent Ampligen (mismatched double- (Prereg.) for the treatment of hepatitis C. Estimated approval: January 2013 stranded RNA) Hemispherx CFS/ME (Prereg.) Boceprevir Schering-Plough (Source: Wolters Kluwer Health). Hepatitis C (Ph. III) What the analysts had to say: Uptake of boceprevir, and fellow Albuferon (albinterferon alfa 2-b) Human Genome Sciences Vicriviroc Schering-Plough HCV protease inhibitor telaprevir, is likely to be robust in both HCV infection (Ph. III) (HIV Infection) Ph. III treatment-experienced and naïve patients due to the fact that they offer an increase in efficacy and a potentially abbreviated treatment Efavirenz/lamivudine/tenofovir Rilpivirine Tibotec disoproxil Matrix HIV-1 infection (Ph. III) course (which also suggests an abbreviated duration of treatment- HIV-1 infection (Prereg.) related side effects). They also represent the most significant advan- Prevnar 13 Motavizumab MedImmune Invasive pneumococcal disease (Adults tage in HCV therapy since the advent of the pegylated RSV (Prereg.) & Infants) (Ph. III) (Peg-Intron from Schering-Plough and Pegasys from Roche). —Noah Pines, EVP, GfK Healthcare

44 MM&M x DECEMBER 2009 x mmm-online.com PIPELINE 2010 Metabolic PRODUCTS GENERATING BUZZ OTHER KEY PRODUCTS IN THE PIPELINE Byetta Once-Weekly ( LAR) /Lilly/ Indication: Type 2 diabetes (Preregistration) ALD 101 Aldagen MK 2866 GTx/Merck What the clinical trials found: Results of a phase III study (DURA- Metabolic disorders (Ph. III) Cachexia (Ph. III) TION-1) that included 295 subjects with type 2 diabetes suggest that exenatide LAR may offer improved blood glucose control over Fluoconolone acetonide Alimera/ HPN 100 Hyperion pSivida Hyperammonemia (Ph. III) marketed Byetta, with similar safety and efficacy. Diabetic macular edema (Ph. III) inThought Revenue forecast: $1.9 billion US, $3.0 billion world- Mitglinide Kissei DiaPep 277 Andromeda Type 2 diabetes (Ph. III) wide, by 2016 Type 1 diabetes (Ph. III) inThought Approvability Index and Comment: 82%. Byetta is inhalation Mankind AI 401 Autoimmune Type 1, 2 diabetes (Prereg.) currently approved as a twice-daily injection for patients with type Type 1 diabetes (Ph. III) 2 diabetes. Although sales have been flat for three years,in Thought MK-0431C Merck expects the once-weekly version to be a success. This formulation Dextromethorphan/ Diabetes (Ph. III) Avanir should win out over not only the twice-daily Byetta, but also Novo Emotional lability, diabetic neuropathies Colestilan Mitsubishi Tanabe Nordisk’s once-daily Victoza (). Estimated approval: June (Ph. III) Hyperphosphatemia (Ph. III) 2011 (Source: Wolters Kluwer Health). Dapagliflozin Bristol-Myers Squibb Dutogliptin Phenomix What the analysts had to say: Doctors are writing fewer prescrip- Type 2 diabetes (Ph. III) Type 2 diabetes (Ph. III) tions for Byetta than in the past, and that may be due to safety BTG Regeneron/Bayer concerns with a lot of diabetes meds. Many may be concerned about Type 2 diabetes (Ph. III) Age-related macular degen. (Ph. III) pancreatitis or are waiting for FDA approval of Byetta LAR. Victoza Diamyd Diamyd Medical Enclomifene Repros is expected to arrive on the US market by third-quarter 2010. Type diabetes mellitus (Ph. III) Hypogonadism (Ph. III) —Dave Jacobson, diabetes practice leader/SVP, Roper Diabetes Ranirestat Dainippon Sumitomo Roche Group, GfK Healthcare Diabetic neuropathies (Ph. III) Type 2 diabetes (Ph. III)

Byetta LAR Eli Lilly Sanofi-Aventis Lorcaserin Arena Diabetes (Ph. III) Type 2 diabetes (Ph. III) Indication: Obesity (Ph. III) Tagatose Spherix The BLOSSOM phase III study Ruboxistaurin Eli Lilly What the clinical trials found: Diabetic retinopathy (Prereg.), Diabetic Type 2 diabetes (Ph. III) met all primary endpoints and FDA benchmarks over one year. In macular edema (Ph. III) Alogliptin Takeda obese patients treated with 10 mg lorcaserin dosed twice daily, 63% Eli Lilly Type 2 diabetes (Prereg.) of patients lost at least 5% of their body weight; with 10 mg lorcaserin Diabetes (Ph. III) Tesamorelin Theratechnologies dosed once daily, 53.1% achieved at least 5% weight loss. Insulin oral spray Generex Lipodystrophy (Prereg.) inThought Revenue forecast: $700 million US, $850 million world- Type 1 diabetes (Ph. III) wide, by 2016 Otelixizumab Tolerx GlaxoSmithKline Type 1 diabetes (Ph. III) inThought Approvability Index and Comment: 67%. Like Vivus’ Type 2 diabetes (Ph. III) Qnexa (phentermine/), lorcaserin is a promising and Vitreosolve VitreoRetinal Diabetic retinopathy (Ph. III) unpartnered obesity medicine. It has demonstrated less efficacy than Qnexa, but also more mild adversities, a profile that will likely make it more broadly used if approved. Estimated approval: March 2011 (Source: Wolters Kluwer Health). 11%, respectively, compared to 1.6% in the placebo group. What the analysts had to say: Lorcaserin efficacy remains modest inThought Revenue forecast: $425 million US, $525 million world- and with higher rates of SAEs vs. placebo. We continue to believe that wide, by 2016 regulatory risk persists with data unlikely to support partnership. inThought Approvability Index and Comment: 72%. Although —Jim Birchenough, MD, Barclays Capital large pharma has shied away from developing obesity medicines lately, several small biotechs have developed promising compounds. Qnexa (phentermine/topiramate) Vivus Vivus’s drug is a combination of two approved agents, phentermine Indication: Obesity (Ph. III) and topiramate. Although likely to be approved, adversities such as What the clinical trials found: The Ph.III EQUIP study showed cognitive impairment, depression and potential liver concerns are once-daily phentermine/topiramate low-dose (3.75 mg/23 mg) and likely to limit use to a subset of obese patients. Estimated approval: full-dose (15 mg/92 mg) produced a mean weight loss of 5.1% and August 2011 (Source: Wolters Kluwer Health).

mmm-online.com x DECEMBER 2009 x MM&M 45 uerosto commodo odionul Rare Disease PRODUCTS GENERATING BUZZ OTHER KEY PRODUCTS IN THE PIPELINE Xiaflex (collagenase)Auxilium Indication: Dupuytren’s contracture (Preregistration) What the clinical trials found: A phase III trial in 35 patients AB Science Thymoglobulin Genzyme Mastocytosis (Ph. III) Myelodysplastic syndromes (Ph. II) showed local injection achieved a 91% therapeutic success rate for the primary endpoint after ≤ 3 injections compared with a 0% Ethyl eicosapentaenoic acid TSH Genzyme Amarin Nontoxic multinodular goiter (Ph. II) response rate in the placebo group. Adverse events were generally Huntington’s disease (Ph. III) mild to moderate. Dimebolin Medivation/Pfizer inThought Revenue forecast: $600 million US, $850 million world- Migalastat Amicus/Shire Huntington’s disease (Ph. III) Fabry’s disease (Ph. III) wide, by 2016 Amantadine Recordati inThought Approvability Index and Comment: 96%. Dupuytren’s AT1001 Amicus Huntington’s disease (Ph. III) Fabry’s disease (Ph. II) contracture is a rare condition, primarily in the elderly, that causes Idebenone Santhera contraction of the fingers. Xiaflex is likely to become a viable option AT2101 Amicus Duchenne muscular dystrophy (Ph. III) Gaucher’s disease (Ph. II) to surgery for patients not only with Dupuytren’s, but also patients HGT-2310 Shire with other rare conditions caused by buildup, including fro- AT2220 Amicus Hunter syndrome (Ph. II) Pompe disease (Ph. II) zen shoulder syndrome and peyronie’s disease. Estimated approval: HGT-1111 Shire Dec. 15, 2009 (Source: Wolters Kluwer Health). PEG-PAL Biomarin Metachromatic leukodystrophy (Ph. III) PKU (Ph. II) What the analysts had to say: Xiaflex is injectable, so safety pro- Firazyr Shire file issues are almost nonexistent. We are picking up on a lot of Celtic Pharma HAE (Ph. III) Brain edema (Ph. III) interest from hand surgeons who use it—they say it will cut into Velaglucerase alfa Shire/Protalix their business. —Ben Weintraub, PhD, director of research, Wolters Ataluren Genzyme Gaucher’s disease type 1 (Prereg.) Kluwer inThought Cystic fibrosis (Ph. III); Duchenne and Becker muscular dystrophy (Ph. II) DX-88 Dyax Genz-112638 oral therapy Indication: Hereditary angioedema (HAE) (Preregistration) Genzyme Gaucher’s disease (Ph. III) What the clinical trials found: Phase III data showed significant improvements in the severity of an HAE attack compared with placebo and good tolerability. Krystexxa (pegloticase) Savient Revenue forecast: $165 million worldwide by 2014, says Phil Nadeau Indication: Gout (Preregistration) of Cowen + Co. What the clinical trials found: Primary data from two phase III trials inThought Approvability Index and Comment: 90%. Although in patients with treatment-failure gout showed clinically meaningful HAE is a rare condition, several drugs are vying for approval and improvements and good tolerability. use. inThought believes that Dyax’s DX-88 is the most promising. inThought Approvability Index and Comment: 90%. Although Others include Viropharma’s approved drug Cinryze, CSL Behring’s gout is a common condition, treatment refractory gout is an orphan Berinert (approved this year), Pharming’s Rhucin and Shire’s icati- indication. Xiaflex is one of two new gout drugs (Takeda’s Uloric bant. Estimated approval date: December 15, 2009 (Source: Wolters was approved this year) that is likely to significantly improve the Kluwer Health). outlook for patients with severe gout. Estimated approval: August What the analysts had to say: The two approved HAE therapies are 2010 (Source: Wolters Kluwer Health). C1-INH inhibitors taken prophylatically. What doctors and patients What the analysts had to say: We think this will be very successful, really want is something that can be put in the medicine chest and but the treatment-refractory population is small. administered when an HAE attack is coming on. —Ben Weintraub, —Geoff Penney, VP, GfK Healthcare PhD, director of research, Wolters Kluwer inThought Validation of Krystexxa batches is progressing well, and FDA-related label and REMS discussions continue to suggest a broad and unre- strictive market opportunity in treatment-failure gout. —Salveen Kochnover, CFA, Collins Stewart

46 MM&M x DECEMBER 2009 x mmm-online.com PIPELINE 2010 Rheumatology PRODUCTS GENERATING BUZZ OTHER KEY PRODUCTS IN THE PIPELINE Prolia (denosumab) Indication: Osteoporosis (Preregistration); bone discorders cancer, (Ph. III) Tissue repair stem cell therapy Hectorol Genzyme Aastrom Biosciences Psoriasis (Ph. II) What the clinical trials found: Phase II studies in patients with Osteonecrosis (Ph. III) advanced have shown that denosumab is as effective as IV bis- Prochymal Genzyme ABT-874 Abbott Crohn’s disease, GVHD (Ph. III) phosphonates at suppressing the ratio of bone turnover markers, with Inflammation (Ph. III), Plaque psoriasis more rapid, sustained absorption and consistent adverse events. (Ph. III) Thymoglobulin Genzyme inThought Revenue forecast: $1.8 billion US, $2.9 billion world- Liver transplant (Ph. II) Masitinib AB Science wide, by 2016 Gastro. stromal disorders, pancreatic Epratuzumab Immunomedics/UCB inThought Approvability Index and Comment: 96%. Probably the cancer (Ph. III) Systemic lupus erythematosus (Ph. III) most exciting developmental drug of 2009, Prolia is a rank-ligand Active Biotech Alicaforsen Isis inhibitor that will compete with bisphosphonates for the treatment MS (Ph. III) Pouchitis, ulcerative colitis (Ph. III) of osteoporosis and in some cancer scenarios. inThought expects Oral dnaJP1 Adeona Voclosporin Isotechnika Prolia will be approved early next April and become a blockbuster. RA (Ph. III) Plaque psoriasis, uveitis (Ph. III)

(Source: Wolters Kluwer Health). Interferon-alpha Amarillo/Hayashi- MK-0822 (odanacatib) Merck What the analysts had to say: As the first biologic in the osteopo- bara Osteoporosis (Ph. III) Sjogren’s syndrome (Ph. III) rosis space, denosumab is expected to provide significant efficacy. Novartis The clinical trials seem to bear that out. Based on what we know Esomeprazole/naproxen MS (Ph. III) AstraZeneca/Pozen about other biologics, this one will be cautiously adopted by physi- Naproxinod NicOx Ankylosing spondylitis, osteoarth., RA cians given the risk profile. Osteoarthritis (Prereg.) (Prereg.) Geoff Penney, VP, category business leader, GfK Healthcare — Fingolimod Novartis BG 12 Idec MS (Ph. III) Benlysta () Human Genome Sciences/GSK MS (Ph. III) Omr-IgG-am OMRIX PEG-interferon B-1a Biogen Idec Indication: Systemic lupus erythematosus (Ph. III) Immunodeficiency disorders (Ph. III) What the clinical trials found: Treatment of 10 mg/kg in addition MS (Ph. III) Prochymal Osiris Biogen Idec/Roche to standard care resulted in a significant improvement in patient Crohn’s disease, GVHD (Ph. III) response after 52 weeks, compared with placebo plus standard of care, , RA (Ph. III) S,S-Reboxetine Pfizer Bristol-Myers Squibb meeting the primary endpoint in the phase III BLISS-76 trial. Fibromyalgia (Ph. III) Revenue forecast: Peak sales of at least $3 billion, says Jim Birch- Renal transplant rej. (Prereg.) Ataluren PTC/Genzyme enough of Barclays Capital Fampridine SR Elan Cystic fibrosis (Ph. III) inThought Approvability Index and Comment: 66%. Drug develop- MS (Prereg.) Mycophenolate mofetil Roche ment for lupus has been littered with failures, but Human Genome’s Genelabs MS (Ph. II/III) drug is on track. The anti-BLyS showed exceptionally strong Systemic lupus erythematosus (Ph. III) Beclometasone oral Soligenix results from its first phase III trial. Although data from a second Genzyme GVHD (Prereg.) phase III trial were somewhat mixed, FDA filing should remain on MS (Ph. III) track for early 2010 (Source: Wolters Kluwer Health). What the analysts had to say: While off-label use of currently available biologics may erode opportunities, I don’t think it will the potential to replace injectable drugs for severe RA with an as Benlysta will have the power of promotion, thanks to GSK’s oral pill. Pfizer’s JAK kinase inhibitor is the lead drug with such marketing muscle. potential. Phase III results presented at October’s American Col- —Geoff Penney, VP, category business leader, GfK Healthcare lege of Rheumatology meeting are very promising (Source: Wolters Kluwer Health). CP 690,550 Pfizer What the analysts had to say: This JAK-inhibitor has a unique Indication: Rheumatoid arthritis (Ph. III) mode of action and will be one of the first oral therapies in the RA What the clinical trials found: Two six-month phase IIb studies market. (The biologics are all self-injection or infusion therapies.) showed rapid and sustained improvement in pain, physical function- It’s going to be interesting to see how quickly patients demand oral ing, fatigue and health-related quality-of-life parameters. therapies and physicians oblige. inThought Comment: Physicians and patients are excited about —Geoff Penney, VP, category business leader, GfK Healthcare

mmm-online.com x DECEMBER 2009 x MM&M 47 PIPeLINE 2010

OTHER KEY PRODUCTS IN THE PIPELINE

NEUROLOGY Asthma (Prereg.)

Pimavanserin ACADIA ONCOLOGY Psychotic disorders (Ph. III) Motesanib Amgen/Millennium Other /GSK NSCL (Ph. III) (Ph. III) AstraZeneca PRODUCTS GENERATING BUZZ Nalmefene Biotie/Lundbeck Colorectal (Ph. III) Alcoholism (Ph. III) AstraZeneca Cladribine tablets Merck Serono Dainippon Sumitomo Thyroid (Ph. III) Bipolar disorder (Ph. III) Indication: Multiple sclerosis (Preregistration) AstraZeneca What the clinical trials found: A clear effect on neurological func- CPI 300 IntelGenx/Cary Prostate (Ph. III) tioning was seen in a two-year crossover study in 24 pairs of disease- Depression (Prereg.) Cell Therapeutics matched patients with chronic MS. Neramexane Merz NHL (Prereg.) inThought Revenue forecast: $150 million US, $350 million world- Tinnitus (Ph. III) Omacetaxine mepesuccinate wide, by 2016 Dimebolin Medivation/Pfizer Chemgenex/Stratagem inThought Approvability Index and Comment: 76%. Injectable Alzheimer’s disease (Ph. III) CML (Prereg.) cladribine has been approved for many years as a cancer drug, but Neurocrine Biosciences Daiichi-Sankyo now oral cladribine is looking promising as a therapy for multiple Insomnia (Prereg.) Pancreatic (Ph. III) sclerosis. Patients and physicians are excited about the potential Organon of an oral medicine that can replace injectable interferons and Insomnia (Ph. III) CLL (Prereg.), AML (Ph. III) Copaxone in MS treatment, but most experts believe that it will be Carisbamate Ortho-McNeil Odanacatib Merck a long time before cladribine and other oral drugs are used as first- Epilepsy (Prereg.) Bone cancer (Ph. III) line MS therapy. Estimated approval: June 2010 (Source: Wolters PGxHealth Motexafin Pharmacyclics Kluwer Health). Depression (Ph. III) Brain (Prereg.) What the analysts had to say: The physician-patient dynamic will be extremely interesting to watch. Neurologists are typically Sanofi-Aventis Oregovomab Quest Therapeutics Insomnia (Prereg.) Ovarian (Ph. III) conservative in terms of decisions, and oral cladribine has some risk factors. We are anxious to see the reaction among MS Vanda Sanofi-Aventis Insomnia (Ph. III) Pancreatic (Ph. III) patients, who are highly knowledgeable about treatment options and accustomed to taking risk with their current . RESPIRATORY BSI 201 Sanofi-Aventis Breast (Ph. III) —Geoff Penney, VP, GfK Healthcare Pollinex Quattro Allergy Thera. Seasonal allergic rhinitis (Ph. III) Sanofi-Aventis Prostate (Ph. III) Gammagard (immune globulin) Baxter Grass pollen allergy vaccine Indication: Alzheimer’s disease (Ph. III) Artu Biologicals Laromustine Vion What the clinical trials found: In a six-month phase II study, Seasonal allergic rhinitis (Prereg.) AML (Prereg.) Gammagard was associated with significant clinical benefits in Ception Triacetyluridine Wellstat patients with AD, with findings indicative of potential efficacy and Oesophagitis (Ph. III) Pancreatic (Ph. III) tolerability. Sinapultide Discovery Labs WOMEN’S HEALTH Neonatal resp. distress synd. (Prereg.) inThought Revenue forecast: $1.6 billion US, $3.0 billion world- Boehringer Ingelheim wide, by 2016 Aclidinium bromide Forest/Almirall Female sexual dysfunction (Ph. III) inThought Approvability Index and Comment: 55%. Gammagard COPD (Ph. III) Cositecan Bionumerik is notable for being the only AD drug that has a greater than 50% Ragweed allergy vaccine Greer Ovarian cancer (Ph. III) probability of approval in the inThought models. Other phase III Seasonal allergic rhinitis (Ph. III) Farletuzumab Morphotek drugs, most notably Elan/Wyeth’s bapineuzumab, have significant Denufosol Inspire Ovarian cancer (Ph. III) challenges to overcome. Still, any successful disease modifying Cystic fibrosis (Ph. III) Patupilone Novartis Alzheimer’s drug would have a major impact on patient care. Gam- Loratadine/ montelukast Merck Ovarian cancer (Ph. III) magard is interesting because intravenous immunoglobulin has Seasonal allergic rhinitis (Ph. III) been approved for many years for the treatment of conditions such Esmirtazapine Organon Mometasone/formoterol Merck Vasomotor symptoms (Ph. III) as reducing the risk of transplant rejection. Estimated approval: Asthma (Prereg.), asthma, COPD (Ph. III) September 2012 (Source: Wolters Kluwer Health). Corifollitropin alfa Organon Indacaterol Novartis/Skye Infertility (Ph. III) What the analysts had to say: The big challenges are expected to COPD (Prereg.), asthma (Ph. III) be cost and availability of the medication, as Gammagard is derived Ospemifene QuartRx Roflumilast Nycomed Vaginal atrophy (Ph. III) from human plasma donors. COPD (Prereg.), asthma (Ph. III) —Geoff Penney, VP, GfK Healthcare Tirapazamine SRI Flutiform SkePharma Cervical cancer (Ph. III)

48 MM&M x DECEMBER 2009 x mmm-online.com