R&D Trends: Non-Insulin Antidiabetics - What opportunities remain for the vast pipeline in the crowded diabetes market?

Introduction

The non-insulins antidiabetic pipeline contains nearly 200 products. Although the current treatment algorithm is crowded, no single drug adequately addresses unmet needs in treatment, and there will be opportunities for pipeline products. Innovation in type 1 diabetes is targeted at preserving beta-cell mass and function, while in type 2 diabetes there are many different mechanistic targets.

Features and benefits

• Comprehensive analysis of the current non-insulin antidiabetic pipeline including type 1 and type 2 products, key mechanisms and developers.
• Establish the minimum acceptable and target product profiles necessary for success in the non-insulins market at different therapy lines.
• Leverage insight into clinical trial design and trends in non-insulin antidiabetics
• Assess future directions in non-insulin therapies in type 1 and type 2 diabetes.

Highlights

The rich pipeline of around 200 clinical candidates will continue to provide new drug classes in diabetes treatment. Incretin mimetics are the largest mechanistic class in the pipeline, following the success of marketed dipeptidyl peptidase-IV (DPP-IV) inhibitors and glucagon-like peptide-1 (GLP-1) agonists.
Non-insulin drug development needs large Phase III clinical trial programs that must meet regulator requirements to show a lack of increased cardiovascular risk, as well as proving non-inferiority against key comparators. This process is costly and means that Big Pharma companies dominate the late-stage non-insulin pipeline.
Type 2 diabetes has novel drugs targeted at beta-cell preservation, as well classes aimed at different steps along the glucose metabolism pathway. Future treatment in type 2 diabetes is likely, at least in the near term, to continue the current approach of stepwise therapy addition and use of combinations.

Your key questions answered

• Datamonitor’s updated, comprehensive overview of drugs, mechanisms and manufacturers in the non-insulin antidiabetics pipeline.
• Assess the remaining market opportunities and barriers to uptake for novel non-insulin therapies in type 1 and type 2 diabetes.
• Identify clinical trial requirements and trends in non-insulin antidiabetics, including efficacy and cardiovascular safety needs.

Table Of Contents

Executive Summary

OVERVIEW
Catalyst
Summary

CLINICAL PIPELINE OVERVIEW
Non-insulin antidiabetics
Type 2 diabetes treatments dominate non-insulins pipeline
Mechanisms of action in the non-insulin antidiabetics pipeline
Broad range of glucose management targets in diabetes
Incretin mimetic classes dominate the pipeline
Mechanisms in the late-stage pipeline
Developers in non-insulin antidiabetics
Big Manufacturers responsible for majority of non-insulins pipeline
Diabetes pipeline attracts small players with single drug focus
Big manufacturers stick with tried and tested drug delivery
Eli Lilly leads Big Pharma involvement in antidiabetics development
Development compounds recently discontinued
Candesartan + pioglitazone (Takeda)
Taspoglutide (Roche/Ipsen)
Anti-CD-3 monoclonal antibodies

TARGET PRODUCT PROFILE
Current gold standard and comparator therapies
First-line comparator: metformin (various manufacturers)
Second-line comparator: Januvia (sitagliptin; Merck & Co.)
Later-line comparator: Byetta (exenatide; Eli Lilly/Amylin)
Target product profile versus current level of attainment

CLINICAL TRIAL DESIGN IN NON-INSULIN ANTIDIABETICS
Clinical endpoint: efficacy
Control of average blood glucose levels
Insulin sensitivity and treatment delay
Blood markers
Weight loss
Safety and side effects in clinical trials
Weight gain
Cardiovascular endpoints
The Bydureon tQT requirement: what does it mean?
Comparators: add-on versus replacement therapy in clinical trials
Future trends in clinical trial design
Safety
Positive macrovascular effects
Combinations
Biomarkers and surrogate endpoints
Comparative effectiveness studies and post-marketing risks

INNOVATIVE EARLY-STAGE APPROACHES
Autoimmune therapies
Diamyd (rhGAD65; Diamyd Medical)
DiaPep277 (Andromeda Biosciences/Teva)
BGP-15 (N-Gene)
Thymoglobulin (Genzyme)
BHT-3021 (Bayhill/Roche)
IBC-VS01 (Joslin Diabetes Center)
Adult mesenchymal stem cells
Anti-inflammatory therapies
Ilaris (canakinumab; Novartis)
XOMA 052 (gevokizumab; Xoma/Servier)
IL1bQb (Cytos Biotechnology)
Triolex (HE3286, Harbor BioSciences)
Alpha-1 antitrypsin
Glucokinase activators
G-protein coupled receptor mechanisms
GPR40 agonists
GPR119 agonists
11-beta-HSD inhibitors
Islet transplantation and neogenesis
Diabecell (Living Cell Technologies)
Pro-Islet-1 (beta-islet cells, human; ViaCyte)
INGAP peptide (Exsulin/Kinexum)

THE FUTURE OF NON-INSULIN DIABETES TREATMENT
Type 1 diabetes
Type 2 diabetes
Type 2 diabetes therapy is, and will remain, complex
Early use of combinations
Increased emphasis on cardiovascular outcomes
Co-morbidities will be used to differentiate patient treatment algorithms

BIBLIOGRAPHY
Journal papers
Websites

APPENDIX
Report methodology