OBESITY DRUGS AND THERAPIES: TECHNOLOGIES AND GLOBAL MARKETS

Transcription

1 OBESITY DRUGS AND THERAPIES: TECHNOLOGIES AND GLOBAL MARKETS HLC188A May 2016 Kim Lawson Project Analyst ISBN: BCC Research 49 Walnut Park, Building 2 Wellesley, MA USA (toll-free within the USA), or (+1) information@bccresearch.com

2 TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY GOAL AND OBJECTIVES 2 SCOPE OF REPORT 2 INTENDED AUDIENCE 3 METHODOLOGY 3 INFORMATION SOURCES 3 ANALYST'S CREDENTIALS 3 RELATED BCC RESEARCH REPORTS 3 BCC RESEARCH WEBSITE 4 DISCLAIMER 4 CHAPTER 2 EXECUTIVE SUMMARY 6 WHERE PROGRESS WAS 7 SUMMARY TABLE GLOBAL MARKET FOR OBESITY TREATMENTS BY TYPE, THROUGH 2021 ($ MILLIONS) SUMMARY FIGURE GLOBAL MARKET FOR OBESITY TREATMENTS BY TYPE, ($ MILLIONS) KEY DRIVERS 11 KEY CHALLENGES 11 KEY TRENDS CHAPTER 3 OBESITY OVERVIEW AND BACKGROUND 14 TABLE 1 BMI CATEGORIES 14 OBESITY EXPLAINED 15 TABLE 2 KEY ADIPOCYTOKINES AND MAIN EFFECTS 16 BIOCHEMISTRY INVOLVED IN OBESITY 17 FIGURE 1 MAIN SIGNALING AREAS TARGETED FOR OBESITY INTERVENTION 19 Neuropeptide Y (NPY) Inhibitors 19 Sympathomimetics 20 Tesofensine 20 Dopamine Antagonists 20 Cannabinoid-1 Receptor (CB1) Antagonists 21 Leptin 21 Bupropion 22 Zonisamide 22 Gastrointestinal Areas of Activity 23 Glucagon-like Peptide-1 Analogues 23 Monoacylglycerol Acyltransferase 2 (MGAT2)-Mediated Enzyme 24 Oxyntomodulin 24 PYY 25 CCK and CCK1R Agonists 25 Ghrelin and Ghrelin Inhibitors 25 Enterostatin and Apolipoprotein A-IV 25 Pancreatic Polypeptide (PP) 26 Amylin and Amylin Analogues 26 Lipase Inhibitors 26

3 Cyclic Nucleotides 27 OBESITY CAUSES 27 Age 27 Genetics 27 Pregnancy 28 Medications 28 Inadequate or Excessive Sleep 28 RELATED CONDITIONS 28 Polycystic Ovary Syndrome (PCOS) 28 Cardiovascular Disease 29 Cancer 29 Binge Eating 30 TABLE 3 MEDICATIONS IN DEVELOPMENT FOR BINGE EATING 30 Diabetes 31 Standard Diabetic Treatments 32 Metformin 32 Sulfonylurea (SU) 33 Thiazolidinedione (TZD) 33 Alpha-Glucosidase Inhibitors 34 Insulin Treatment 34 Long-Acting Insulin 34 Intermediate-Acting Insulin 35 Regular or Short-Acting Insulin 35 Rapid-Acting Insulin 35 FIGURE 2 ADA'S STANDARD OF MEDICAL CARE IN DIABETES, Incretin Therapies 36 TABLE 4 COMMERCIALIZED INCRETIN THERAPY 38 TABLE 5 ADVANTAGES TO ADDING INCRETIN THERAPY 39 Exenatide 39 Liraglutide 41 Dulaglutide 42 Albiglutide 43 Lixisenatide 43 DATA ON INCRETIN USE 44 FIGURE 3 PERCENTAGE OF DISPENSED PRESCRIPTIONS FOR GLP-1 RECEPTOR AGONISTS, 2012 (%) GLP-1's Future in Obesity 45 TABLE 6 GLP-1 RECEPTOR AGONISTS IN LATE-STAGE DEVELOPMENT 46 TABLE 7 GLP-1 RECEPTOR AGONISTS IN EARLY-STAGE DEVELOPMENT CHAPTER 4 MARKET OVERVIEW AND FORECAST 49 OVERALL PHARMA MARKET 49 TABLE 8 REVENUE OF TOP PHARMA COMPANIES, 2014 ($ BILLIONS) 49 FIGURE 4 GLOBAL MARKET SHARE OF PHARMACEUTICAL DRUGS BY REGION, 2014 AND 2019 DIABETES AS SALES TERRITORY 51 BIOLOGICS AND GLP-1 RECEPTOR AGONIST PRODUCTION 52 GROWTH FACTORS 54 50

4 GENE THERAPY 54 RECOMBINANT PROTEINS 54 MONOCLONAL ANTIBODIES 54 BIOLOGIC LANDSCAPE 54 TABLE 9 BIOLOGICS IN DEVELOPMENT IN THE U.S. BY THERAPEUTIC CATEGORY, 2013 OBESITY TREATMENTS WITHIN THE PHARMA LANDSCAPE 55 MARKET LANDSCAPE 56 DEALS IN THE OBESITY MARKET 57 TABLE 10 KEY AGREEMENTS AROUND OBESITY TREATMENTS 58 BRIEF HISTORY OF OBESITY DRUGS 61 RECENT TRENDS AND OBESITY THERAPY APPROVALS 61 TABLE 11 TIMELINE OF OBESITY MEDICATION APPROVALS 62 FDA-APPROVED ANTI-OBESITY MEDICATIONS DESCRIBED 63 Desoxyephedrine 63 Phendimetrazine 63 Benzphetamine 63 Diethylpropion 64 Orlistat (Xenical) 64 Phentermine and Topiramate Extended-Release (Qsymia) 64 Lorcaserin Hydrochloride (Belviq) 65 Naltrexone and Bupropion Extended-Release Tablets (Contrave/Mysimba) Liraglutide (Saxenda) 67 Cetilistat (Oblean-Approved in Japan Only) 68 TABLE 12 FDA-APPROVED LONGER-TERM ANTI-OBESITY MEDICATIONS' MECHANISM OF ACTION AND WEIGHT-LOSS STATISTICS IN CLINICAL TRIALS FIGURE 5 NUMBER OF COMMERCIALIZED OBESITY DRUGS AND DEVICE THERAPEUTICS, 2016 AND 2021 (UNITS) FIGURE 6 NUMBER OF COMMERCIALIZED BARIATRIC SURGERIES MINUS BANDS AND BALLOONS, 2016 AND 2021 (UNITS) FIGURE 7 NUMBER OF COMMERCIALIZED OBESITY THERAPIES BY MECHANISM OF ACTION, 2016 AND 2021 (%) FIGURE 8 GLOBAL MARKET FOR COMMERCIALIZED OBESITY THERAPIES BY MECHANISM OF ACTION, 2016 AND 2021 (%) FIGURE 9 NUMBER OF COMMERCIALIZED OBESITY TREATMENTS BY DOSING TYPE, 2016 AND 2021 (%) FIGURE 10 GLOBAL MARKET OF COMMERCIALIZED OBESITY TREATMENTS BY DOSING TYPE, 2016 AND 2021 (%) WEIGHT LOSS THROUGH SURGERY 76 Gastric Bypass 76 Biliopancreatic Diversion with Duodenal Switch (BPD/DS) Gastric Bypass Sleeve Gastrectomy 77 Adjustable Gastric Band 77 SURGERY OUTCOMES 78 TABLE 13 PROS AND CONS OF BARIATRIC SURGERY 79 FIGURE 11 FOUR MOST COMMON U.S. BARIATRIC PROCEDURES 79 TABLE 14 DIFFERENCES BETWEEN THE OBESITY SURGERIES

5 ACCESS TO WEIGHT-LOSS SURGERY 82 FIGURE 12 CASE MIX OF BARIATRIC SURGERIES IN THE U.S., 2014 (%) 84 GASTRIC BANDS AND BALLOONS DETAILED 85 TABLE 15 TIMELINE OF OBESITY DEVICE APPROVALS 85 Lap-Band Gastric Banding System 85 Realize Gastric Band 86 Maestro Rechargeable System 86 FIGURE 13 MAESTRO RECHARGEABLE SYSTEM 87 BALLOONS AS PART OF BANDS 88 ReShape Integrated Dual Balloon System 89 ORBERA Intragastric Balloon System 89 FIGURE 14 NUMBER OF COMMERCIALIZED OBESITY DEVICES*, 2016 AND 2021 (%) 90 SURGICAL USAGE AND SPENDING 91 TABLE 16 BARIATRIC SURGERY SPENDING IN EUROPE, CHAPTER 5 DEVELOPMENT PIPELINE DETAILED 94 DEVICE APPROVAL PROCESS 94 BENEFIT/RISK MODEL FOR FDA CLINICAL TRIALS 94 TABLE 17 FDA BENEFIT-RISK ASSESSMENT FOR OBESITY DEVICE CLINICAL TRIALS 95 TABLE 18 TARGET EFFECTIVENESS LEVELS FOR TOTAL BODY WEIGHT LOST (TBL) (%) MOVING OBESITY DRUGS THROUGH THE FDA 97 PATENTS 98 DEVELOPMENT PIPELINE 100 TABLE 19 OBESITY DRUGS IN DEVELOPMENT 100 KEY OBESITY DRUGS IN DEVELOPMENT 101 ZGN-440 (Beloranib) 101 Setmelanotide (RM-493) 102 Semaglutide (NN9536-GLP-1 Analogue) 102 HM11260C/Efpeglenatide (Glucagon-like Peptide-1 Analogue) 103 LAPSGLP/GCG-HM12525A (Glucagon-like Peptide-1 Analogue/Glucagon Analogue) ALS L1023 (Korean Clinical Trial) 103 ZP PL Merck and NGM Biopharmaceuticals and NGM313, NGM386 and NGM395 MOD-6031 (Long-Acting Oxyntomodulin) 105 Tesofensine 106 Gelesis OBESITY DEVICES IN DEVELOPMENT 108 Obalon Therapeutics' Obalon balloon 108 Aspire Bariatrics' AspireAssist 108 SatiSphere System 109 Sensor Monitored Alimentary Restriction Therapy (SMART) 110 Spatz3 Adjustable Balloon 110 OTHER DEVICES 111 GI Dyamics' EndoBarrier

6 Allurion Technologies' Elipse Gastric Balloon 111 MetaCure's Diamond System 111 BAROnova's TransPyloric Shuttle (TPS) 112 DEVELOPMENT CASE STUDY: ZAFGEN 113 PROMISING NOVEL RESEARCH 114 OBESITY DRUGS IN EARLY RESEARCH 114 SYM Glycine-Beta Muricholic Acid (Gly-MCA) 115 Metformin 115 Miglitol 115 Fibroblast Growth Factor 21 (FGF21) 116 Amlexanox 116 p75 Neurotrophin Receptor (NTR) 116 Transcranial Direct Current Stimulation 117 Perforin and Dendritic Cells 117 TABLE 20 OBESITY DRUG AND DEVICE DEVELOPMENT RESOURCES 117 CHAPTER 6 COMPANY PROFILES 121 ALLURION TECHNOLOGIES 121 A.M.I. GMBH AUSTRIA 121 AMUNIX 122 APOLLO ENDOSURGERY INC. 123 ARENA PHARMACEUTICALS INC. 124 ARISAPH 125 ASPIRE BARIATRICS INC. 126 ASTRAZENECA 127 ATHERSYS INC. 127 BARONOVA INC. 128 BECTON, DICKINSON AND CO. 128 BFKW 128 BOEHRINGER INGELHEIM GMBH 129 BRISTOL-MYERS SQUIBB 130 CIRCUIT THERAPEUTICS INC. 131 CONJUCHEM 131 C.R. BARD INC. 132 DONG-A SOCIO HOLDINGS 132 EISAI 133 ELI LILLY AND CO. 133 EMISPHERE TECHNOLOGIES INC. 134 ENDOBETIX 136 ENDOSPHERE INC. 136 ENTEROMEDICS INC. 137 ETHICON ENDO-SURGERY LLC 138 GELESIS INC. 139 GI DYNAMICS INC. 140 GLAXOSMITHKLINE PLC 141 HANMI PHARMACEUTICAL CO. LTD. 142

7 HELIOSCOPIE 143 INTARCIA THERAPEUTICS INC. 144 INTRAPACE INC. 145 INTREXON CORP. 145 JOHNSON & JOHNSON 146 LIGAND PHARMACEUTICALS INC. 147 LIGHTLAKE THERAPEUTICS INC. 147 MANNKIND CORP. 148 MEDTRONIC 149 MERCK 149 MERRION PHARMACEUTICALS LTD. 151 METACURE GERMANY GMBH 152 MID-MEDICAL INNOVATION DEVELOPMENT 152 MITSUBISHI TANABE PHARMA CORP. 153 NEOTHETICS INC. 154 NGM BIOPHARMACEUTICALS INC. 155 NORGINE B.V. 155 NOVARTIS INTERNATIONAL AG 156 NOVO NORDISK A/S 156 OBALON THERAPEUTICS 158 ONCIOMED 159 ONO PHARMACEUTICALS 159 OPKO BIOLOGICS 160 ORAMED PHARMACEUTICALS 161 OREXIGEN 161 PALATIN TECHNOLOGIES INC. 163 PFIZER 163 PHASEBIO PHARMACEUTICALS INC. 165 PLENSAT INC. 165 RESHAPE MEDICAL INC. 166 RHYTHM 166 ROCHE 167 SANIONA 168 SANOFI 169 SATRX LLC 170 SCIENTIFIC INTAKE 171 SHIRE PHARMACEUTICALS INC. 171 SPATZ FGIA 172 SYMMETRY THERAPEUTICS INC. 173 TAKEDA PHARMACEUTICAL CO. LTD. 173 TRANSITION THERAPEUTICS INC. 174 TULIP MEDICAL 175 VALENTX 176 VIVUS INC. 176 VTV THERAPEUTICS INC. 178 W.L. GORE AND ASSOCIATES 178 ZAFGEN 179

8 ZEALAND PHARMA A/S 180 ZOSANO PHARMA CORP. 181

9 LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL MARKET FOR OBESITY TREATMENTS BY TYPE, THROUGH 2021 ($ MILLIONS) TABLE 1 BMI CATEGORIES 14 TABLE 2 KEY ADIPOCYTOKINES AND MAIN EFFECTS 16 TABLE 3 MEDICATIONS IN DEVELOPMENT FOR BINGE EATING 30 TABLE 4 COMMERCIALIZED INCRETIN THERAPY 38 TABLE 5 ADVANTAGES TO ADDING INCRETIN THERAPY 39 TABLE 6 GLP-1 RECEPTOR AGONISTS IN LATE-STAGE DEVELOPMENT 46 TABLE 7 GLP-1 RECEPTOR AGONISTS IN EARLY-STAGE DEVELOPMENT 46 TABLE 8 REVENUE OF TOP PHARMA COMPANIES, 2014 ($ BILLIONS) 49 TABLE 9 BIOLOGICS IN DEVELOPMENT IN THE U.S. BY THERAPEUTIC CATEGORY, 2013 TABLE 10 KEY AGREEMENTS AROUND OBESITY TREATMENTS 58 TABLE 11 TIMELINE OF OBESITY MEDICATION APPROVALS 62 TABLE 12 FDA-APPROVED LONGER-TERM ANTI-OBESITY MEDICATIONS' MECHANISM OF ACTION AND WEIGHT-LOSS STATISTICS IN CLINICAL TRIALS TABLE 13 PROS AND CONS OF BARIATRIC SURGERY 79 TABLE 14 DIFFERENCES BETWEEN THE OBESITY SURGERIES 81 TABLE 15 TIMELINE OF OBESITY DEVICE APPROVALS 85 TABLE 16 BARIATRIC SURGERY SPENDING IN EUROPE, TABLE 17 FDA BENEFIT-RISK ASSESSMENT FOR OBESITY DEVICE CLINICAL TRIALS 95 TABLE 18 TARGET EFFECTIVENESS LEVELS FOR TOTAL BODY WEIGHT LOST (TBL) (%) 97 TABLE 19 OBESITY DRUGS IN DEVELOPMENT 100 TABLE 20 OBESITY DRUG AND DEVICE DEVELOPMENT RESOURCES

10 LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL MARKET FOR OBESITY TREATMENTS BY TYPE, ($ MILLIONS) FIGURE 1 MAIN SIGNALING AREAS TARGETED FOR OBESITY INTERVENTION 19 FIGURE 2 ADA'S STANDARD OF MEDICAL CARE IN DIABETES, FIGURE 3 PERCENTAGE OF DISPENSED PRESCRIPTIONS FOR GLP-1 RECEPTOR AGONISTS, 2012 (%) FIGURE 4 GLOBAL MARKET SHARE OF PHARMACEUTICAL DRUGS BY REGION, 2014 AND 2019 FIGURE 5 NUMBER OF COMMERCIALIZED OBESITY DRUGS AND DEVICE THERAPEUTICS, 2016 AND 2021 (UNITS) FIGURE 6 NUMBER OF COMMERCIALIZED BARIATRIC SURGERIES MINUS BANDS AND BALLOONS, 2016 AND 2021 (UNITS) FIGURE 7 NUMBER OF COMMERCIALIZED OBESITY THERAPIES BY MECHANISM OF ACTION, 2016 AND 2021 (%) FIGURE 8 GLOBAL MARKET FOR COMMERCIALIZED OBESITY THERAPIES BY MECHANISM OF ACTION, 2016 AND 2021 (%) FIGURE 9 NUMBER OF COMMERCIALIZED OBESITY TREATMENTS BY DOSING TYPE, 2016 AND 2021 (%) FIGURE 10 GLOBAL MARKET OF COMMERCIALIZED OBESITY TREATMENTS BY DOSING TYPE, 2016 AND 2021 (%) FIGURE 11 FOUR MOST COMMON U.S. BARIATRIC PROCEDURES 79 FIGURE 12 CASE MIX OF BARIATRIC SURGERIES IN THE U.S., 2014 (%) 84 FIGURE 13 MAESTRO RECHARGEABLE SYSTEM 87 FIGURE 14 NUMBER OF COMMERCIALIZED OBESITY DEVICES*, 2016 AND 2021 (%)