The report is set to make interesting reading for companies developing diabetic drugs So significant is the market opportunity that many small biopharmaceutical firms are springing up to meet this challenge, dedicating their entire R&D efforts to diabetes alone.
Diabetes represents a large and growing unmet medical need. In the United States, more than 11 million people are diagnosed with diabetes, and a similar number of patients are thought to be undiagnosed. Disease prevalence is on the rise, as are epidemic rates of obesity. Diabetes is associated with severe comoroid conditions including cardiovascular disease, blindness, limb loss and kidney failure and is among the most costly diseases.
New technologies and drug classes for the treatment of diabetes are being developed, As a result it has become a market brimming with opportunities and increasing competition.
According to IMS data, the global market for oral diabetes treatments exceeded $4.5 billion (€3.4 billion) in 2004. The global market for insulin approximated $3 billion in 2003. In the United States, the generic entry of Metformin has caused total revenues from the class to moderate to approximately the 6 per cent level in 2003, and total revenues from the class are expected to decline in 2004 by about 6 per cent, despite 5 per cent expected prescription growth, due to more generic entries.
The survey, co-ordinated by Goldman Sachs (GS), has devoted a lot of attention to Amylin's Exenatide is well poised for a solid launch assuming potential approval in the first half of 2005. The study found that 70 per cent of clinicians indicated that between 10 per cent and 40 per cent of their patients would be candidates for Exenatide therapy.
The survey revealed that with small penetration in the oral segment, projected sales of Exanatide could grow from approximately $75 million in 2005 to $947 million by 2008, reflecting a 7 per cent overall market penetration, and roughly a 14 per cent penetration of the projected patient population inadequately responding to oral therapy.
GS however outlined the key risks that were to be expected. Delays or even a failure to obtain approval of Exenatide, or slower than anticipated commercial ramp could affect sales of the drug by as much as 40 per cent.
Developed by Amylin through collaboration with Eli Lilly, Exenatide is an incretin mimetic, administered by a twice-daily fixed-dose injection. Clinical studies have suggested that Exenatide does not cause hypoglycaemia. The most common side effect observed with exenatide was transient mild nausea.
The report went on to detail several companies, which are developing TZD's to address one or more specific isoforms of the receptor, enhancing efficacy and/or potentially lowering side effects. For example, PPAR (Peroxisome Proliferators Activated Receptors) alpha is mainly expressed in the liver and is thought to mediate positive cardiovascular effects, such as lowering triglyceride levels and increasing high-density lipoprotein levels. In addition to the thiazolidinediones, other classes of non-TZD compounds, designed to act as partial agonists or antagonists of the PPAR gamma, in a tissue specific manner are also in development.
New thiazolidinediones, specifically dual/pan PPAR's have the potential for greater efficacy and improved side effects and it is these reasons that GS predict great things. Avendia (GlaxoSmithKline) and Actos (Takeda/Eli Lilly) are the only commercially available PPAR's which have been commercially successful. These agents act mainly on the gamma isoform of the peroxisome proliferator-activated receptor (PPARy). This receptor is found in adipose, cardiac skeletal muscle, liver and placental tissues.
Other dual/pan PPAR's in the pipeline include Bristol Myers Squibb's Muraglitizar, which is been developed in conjunction with Merck. The agent is currently in Phase III trials and is expected to be looking for a potential early 2005 filing and estimates peak sales, discounted for risk, of approximately $500 million.
Eli Lilly is developing Naveglitizar, a dual-acting PPAR. Phase II studies are on hold pending carcinogenicity studies in rat models. Phase III studies could resume in 2006, depending on the outcomes.
Roche's R-483 is a predominantly PPAR-gamma activator which showed decent efficacy in Phase II studies. Following guidance from the FDA on the whole class regarding safety and toxicity, Phase III trials are on hold until long-term toxicity studies are completed in second half of 2005. Assuming continued development, GS estimate a potential 2008 launch.