Author: Peter Norman, MBA, PhD
CHAPTER 1
INTRODUCTION 1
1.1. What is Diabetes? 1
Type I Diabetes 1
Type II Diabetes 2
1.2. Diabetic Complications 2
1.3. The Need for Improved Disease Control 3
CHAPTER 2
DIABETES 5
2.1. Pathophysiology 5
2.2. Diagnosis 6
2.3. Incidence and Prevalence 6
Gestational Diabetes 7
Early Onset Diabetes 7
Metabolic Syndrome 7
Other Causes of Diabetes 8
2.4. Current Treatment Options 8
CHAPTER 3
CURRENTLY MARKETED THERAPIES 9
3.1. Introduction 9
3.2. Insulin 9
Recombinant Insulins 10
Insulin Analogs 10
3.3. Metformin 11
3.4. KATP Blockers 12
Sulfonylureas 12
Non-Sulfonylureas 13
3.5. PPAR Agonists 14
3.6. Alpha−Glucosidase Inhibitors 14
3.7. Incretin Modulators 15
Peptide Agonists 15
DPP IV Inhibitors 15
3.8. Combination Products 16
3.9. Market Breakdown 17
CHAPTER 4
DEVELOPMENT PIPELINES 19
4.1. Introduction 19
4.2. Established Approaches 19
Insulin, Analogs, and Formulations 20
Pharmacodynamic Approaches for Improved Control of Plasma Insulin 22
Fast Release 22
VIAject 22
Long Acting 22
Degludec 22
FT-105 24
Sustained Control 24
Degludec Plus 24
LY-2605541 25
Alternative Delivery Routes for Insulin 25
Inhaled 25
Afrezza 26
Intranasal 27
Oral 28
Oral-lyn 29
IN-105 29
AI-401 29
Transdermal 30
Absorption Enhancing 30
PPAR Agonists 31
PPARγ Agonists 32
PPARδ Agonists 33
Dual PPAR α/γ Agonists 34
Indeglitazar: A Pan-PPAR Agonist 35
Other, Non-Incretin, Approaches 35
Mitiglinide 36
Avandastat 36
Imeglimin 36
GLP-1 Analogs 37
Exenatide Formulations 38
Bydureon 38
Novel GLP-1 Analogs 39
Taspoglutide 41
Lixisenatide 43
Albiglutide 43
Dulaglutide 43
Other GLP-1 Agonists in Clinical Development 44
GLP-1 Modulator 45
DPP IV Inhibitors 45
Phase III DPP IV Inhibitors 48
Linagliptin 48
Dutogliptin 50
SK-0403 51
Teneligliptin 51
Gemigliptin 51
Phase II DPP IV Inhibitors 51
4.3. New Approaches 52
SGLT2 Inhibition 52
Dapagliflozin 54
Canagliflozin 55
ASP-1941 56
BI-10773 and BI-44847 56
RG-7201 56
LX-4211 56
TS-071 57
ISIS-388626 57
Kissei, GlaxoSmithKline SGLT Inhibitors 57
Glucokinase Activators 58
AZD-1656 and AZD-6370 59
LY-2599506 60
AMG-151 60
TTP-355 and TTP-399 60
Phase I Compounds 61
11β-Hydroxysteroid Dehydrogenase 1 Inhibitors 61
INCB-13739 63
Roche 63
JTT-654 63
AstraZeneca 64
HSD-016 64
Amgen 64
PTP1B Inhibitors 64
ISIS-113715 65
TransTech Pharma’s TTP-814 65
GPR119 Agonists 66
FFA1 Agonists 68
DGAT-1 Inhibitors 68
SCD1 Inhibitors 69
GPBA Agonists 70
Fructose Bisphosphatase Inhibitors 71
Glycogen Phosphorylase Inhibitors 72
AMPKa Modulators 73
SIRT1 Activators 74
Other Oral Agents 75
D-Tagatose 76
Phase II Agents 77
Phase I Agents 78
Biological Agents 78
Anti-CD3 Antibodies 80
Teplizumab 80
Otelixizumab 80
DiaPep277 81
Diamyd’s Vaccines 81
IL-1 Antagonists 81
Bayhill Therapeutics/Genentech’s RG-7426 82
CHAPTER 5
COMPANY PROFILES 83
5.1. Introduction 83
5.2. Major Players 83
Eli Lilly 83
GlaxoSmithKline 85
Merck 86
Novo Nordisk 87
sanofi-aventis 88
Takeda 89
5.3. Emerging Players 90
Amgen 90
Astellas 91
AstraZeneca 91
Boehringer Ingelheim 92
Bristol-Myers Squibb 93
Novartis 95
Pfizer 95
Roche 96
5.4. Specialist Companies 97
Amylin 97
Arisaph Pharmaceuticals 98
Biodel 99
DARA BioSciences 99
Diabetology 100
DiaMedica 101
Diasome Pharmaceuticals 102
Ipsen 102
Lexicon Therapeutics 103
Metabolex 103
Phenomix 104
Piramal Life Sciences 104
Poxel 105
Syndexa Pharmaceuticals 106
Theracos 106
TransTech Pharma 106
CHAPTER 6
MARKET OUTLOOK 109
6.1. Introduction 109
6.2. The Impact of Generics 110
6.3. The Impact of New Therapies 110
Injectable Agents 112
Oral Agents 113
6.4. Market Development 114
CHAPTER 7
EXPERT INTERVIEWS 115
Peter Kurtzhals, PhD
Senior Vice President and Head of Diabetes Research
Novo Nordisk 115
Pascale Malgouyres, PharmD
Business Development and Marketing Director
Poxel 115
Harold E. Van Wart, PhD
President and Chief Executive Officer
Metabolex 115
Type I Diabetes 115
Type II Diabetes 116
REFERENCES 123
GLOSSARY 131
COMPANY INDEX 133