There are a number of molecules currently in development for the treatment of diabetes. The annually increasing prevalence and incidence of diabetes will be the key driving factors for the growth in the value of the diabetes market over the next few years.
Products currently in the market do not serve the unmet need that exists in terms of safety and patient compliance and so the market continues to present opportunities for stronger pipeline candidates. However, for a company to capture this unmet need, it will need to overcome prevailing product weaknesses and adverse effects. These are the biggest challenges currently hindering most pipeline products.
Drugs targeting the incretin system such as dipeptidyl peptidase-IV (DPP-IV) inhibitors are likely to account for the biggest share of the growing market due to their high safety and efficacy profiles. Incretin mimetics Glucagon-like-1 (GLP-1) agonists will also be able to garner a significant share of the diabetes market.
GlobalData research has found that there are over 238 molecules in various stages of the clinical trial pipeline. The late stage pipeline includes some first-in-class and promising drugs such as canagliflozin and D-Tagatose. The mechanism of action of these molecules differs from those already being marketed. If a molecule that has better efficacy and safety profiles than the best currently available treatment regimen in the type 2 diabetes market is developed, that drug will become a blockbuster and will have the potential to tap the market’s unmet need.
The major new classes of drugs include SGLT-2 inhibitors, 11β HSD inhibitors, CCR2 antagonists, selective inhibitors of fructose 1,6-bisphosphatase, immune modulators, cortisol synthesis inhibitors, interleukin-1β antagonists, gastrin-releasing peptide (GRP) receptor agonists, GPR 119 agonists,TLR-4 receptor agonists, FXR antagonists and GSK-3 inhibitors. The late stage pipeline also has a number of me-too molecules such as alogliptin, Bydureon, lixisenatide and Syncria from DPP4 inhibitors and GLP-1 agonists respectively. A competitive price war is expected when these drugs enter the market, as they will target the same patients as the first generation drugs.
There are a number of new formulations of insulin in development, some of which aim to provide more sustained control of insulin levels and more rapid elevation of insulin plasma concentrations. Research activities are also ongoing for the development of insulin formulations for delivery by routes other than injection. Three oral formulations and two related sustained-release formulations of insulin are currently in Phase III. Novo Nordisk is also conducting Phase III trials of its two new ultra long acting formulations of insulin, degludec and degludecplus. They are expected to enter the market in the near future. In addition, ultra-fast-release formulations (Biodel’s VIAject) have been filed for FDA approval.
There are currently two GLP-1 analogs approved for the treatment of type 2 diabetes and many more GLP-1 analogs in clinical development. These include several alternative formulations of exenatide with the extended-release formulation Bydureon (designed for weekly administration). It is planned to be refiled for FDA approval in the second half of 2011 as a once-weekly diabetes drug. GLP-1 analogs such as dulaglutide and albiglutide, along with a modified form of exenatide (lixisenatide), are in Phase III. Lixisenatide and albiglutide are also under investigation in Phase III trials for type 2 diabetes and are expected to come to the market in the near future.
The development of orally administered DPP4 inhibitors remains an area of choice among pharmaceutical companies due to their better efficacy and safety profiles compared to approved oral agents TZDs and Sulfonylurea. Approximately 20 molecules are under development in various stages of clinical trial and five agents have already been approved and launched.
Activators of glucokinase are also first-in-class drugs. There are currently a number of GK activators in the early stages of clinical development. Another novel class of drug in development is 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors which are in Phase I and Phase II.
The early stage clinical pipeline in diabetes has number of novel targets such as GPCRs, GPR119, FFA1 and TGR5. The most prominent among these is the development of GPR119 agonists. GlaxoSmithKline is also developing another novel class of molecules called SIRT1 inhibitors for the treatment of diabetes. Other novel classes of molecules in development include FFA1 receptor agonists, TGR5 agonists, glycogen phosphorylase inhibitor, antisepses inhibitors and interleukin-1 receptor antagonists.