Diabetes Drug Update

Phase II

• Astellas Pharma presented results from a Phase II study of its ASP1941, a selective SGLT2 inhibitor that blocks the reabsorption of glucose into the kidney and excretes it into the urine. The study of 361 Japanese subjects with Type II diabetes showed dose related and statistically significant decreases in HbA1c compared to baseline and against placebo of up to 1.3% reaching a maximum at the 50 mg dose. Based on the results, 50 mg has been selected as the dose for the ongoing Phase III program in Japan, which has a clinicaltrials.gov~ identifier of NCT01054092.

• Lexicon Pharmaceuticals announced Phase IIa clinical trial results for its LX4211, a dual SGLT2 and SGLT1 inhibitor, showing improved glycemic control and positive trends in cardiovascular and metabolic parameters after 28 days of dosing in Type II diabetes subjects. The http://clinicaltrials.gov identifier for this trial is NCT00962065.

Phase III

• Boehringer Ingelheim announced positive data from four Phase III clinical trials on its DPP-4 inhibitor linagliptin for the treatment of Type II diabetes. Linagliptin showed statistically significant reductions in HbA1c versus placebo, and in combination with metformin, metformin and sulphonylurea, and pioglitazone. The http://clinicaltrials.gov identifiers are NCT00621140, NCT00622284, NCT00602472, and NCT00641043, respectively.

FDA Response

• Amylin Pharmaceuticals, Eli Lilly, and Alkermes replied to the FDA's complete response letter to its NDA submission for Bydureon, an extended-release injectable suspension of exenatide, the active ingredient in Byetta, an already approved drug for Type II diabetes. Both Bydureon and Byetta are glucagon-like peptide receptor agonists. The FDA's response letter asked for finalized product labeling with an accompanying REMS and a clarification to its manufacturing processes. The FDA has an action date of October 22 to review. The http://clinicaltrials.gov identifier for the DURATION 5 trial is NCT00877890.

Postmarket

• NovoNordisk announced it has recruited the 60,000th patient into its observational study to investigate insulins when used in clinical practice in diabetics previously using anti-diabetic medication and switching to insulin under a physician's discretion. The insulins being studied are all NovoNordisk products. The results are anticipated in 2011. Study locations are Africa, Asia, South America, and Europe. It has a http://clinicaltrials.gov identifier of NCT00869908.

• An FDA Advisory Committee voted to keep GlaxoSmithKline's Avandia diabetes drug on the market with increased labeling requirements to caution on potential cardiovascular safety risks. At press time, FDA had not announced whether it will follow the panel's advice or withdraw the drug from the market. However, the FDA did put the TIDE postmarketing trial (see Business News for more on TIDE) on partial clinical hold, which means no new subjects can be enrolled in the trial. The FDA has asked GSK to update investigators, IRBs, and ECs on the safety information presented at the meeting so it can be incorporated into existing informed consent materials.

• Pharmacy benefit management company Medco Health Solutions conducted a retrospective analysis of its pharmacy and medical claims data of more than 786,000 adult patients with Type II diabetes from January 2007 to June 2009. The results found that patients initiating therapy for Januvia, Byetta or other oral antidiabetic medications did not increase the risk of acute pancreatitis. However, the risk for acute pancreatitis is 91% higher for all diabetic groups vs. nondiabetics.

Business News

• In an almost three-month span, Metabolex announced collaborations and agreements with Takeda, Ortho-McNeil, and Sanofi-Aventis for various novel products in development for Type II diabetes.

• Because of the more recent cardiovascular safety concerns of Avandia, the Indian government ordered GSK to halt Phase IV trials ongoing there. Communicating through Quintiles, the CRO running the TIDE trial in that country, the Drug Controller General of India requested on June 30 that the trial be placed on hold. TIDE is a comparative trial of Avandia and Actos (see http://clinicaltrials.gov identifier NCT00879970).

• PhRMA's recent Medicines in Development report listed over 235 medicines to treat diabetes and related conditions. Of those, 144 were for Type II diabetes, and 24 for Type I. The following pharma companies have the most drugs in development for Type II diabetes:

• GlaxoSmithKline (12)

• Merck (11)

• AstraZeneca and Eli Lilly (10)

• NovoNordisk and Roche (8)

• Johnson & Johnson (6)