Washington Editor

Amylin Pharmaceuticals Inc. and partner Eli Lilly and Co. released favorable data from a 500-patient study comparing their diabetes candidate, exenatide, to insulin glargine in patients with Type II diabetes.

Successful completion of the trial triggered a $5 million milestone payment from Indianapolis-based Lilly to Amylin, a San Diego-based firm.

Indeed, patients in both the exenatide and glargine groups achieved similar degrees of glycemic control. Also, patients in the exenatide group lost an average of five pounds, compared to glargine patients, who gained an average of three pounds. It is the first trial in which exenatide was studied head-to-head with insulin.

Eric Shearin, Amylin's spokesman, told BioWorld Today the partners have not said whether the 500-patient non-inferiority trial will be used in relationship to the new drug application filed in June for use of exenatide in Type II diabetes. (See BioWorld Today, November 26, 2003, and July 1, 2004.)

The FDA is expected to provide comment by late August on the NDA.

Exenatide (synthetic exendin-4), the first drug candidate in a new class of drugs called incretin mimetics, was in-licensed by Amylin from an individual researcher, who worked on it at an early development stage. Exenatide, like the human incretin hormone GLP-1, has effects on multiple organs that work in concert to improve blood sugar.

In the recent trial, the firms sought to compare exenatide with insulin glargine, a human insulin analogue, in patients who have failed to control their diabetes on a combination of sulfonylurea and metformin. Participants were randomized to receive either a variable dose of insulin glargine at bedtime or a fixed dose of exenatide twice daily just before breakfast and dinner in addition to their current oral therapies.

The primary objective was to achieve comparable glycemic response between the two groups, as evaluated by a change in A1C levels from baseline. Additional endpoints of the study included effects on weight, incidence of hypoglycemia, safety and tolerability.

Beyond weight control, study results demonstrated that both exenatide and insulin glargine patients achieved similar A1C reductions, with endpoint A1Cs of 7.2 percent for both groups at the end of the study. Overall, the incidence of mild to moderate hypoglycemia was similar in both groups, and the most common adverse event reported was mild to moderate nausea, which occurred most frequently early in the study, the companies said.

Meanwhile, the Amylin-Lilly NDA includes favorable data from the "three amigos" Phase III pivotal program for the twice-daily injectable formulation. Each of the studies met primary glucose-control endpoints as measured by hemoglobin A1C, which reflected average glucose levels over the prior three- to four-month period. The average reduction in A1C across the program in patients completing the studies on the highest dose of exenatide (10 micrograms twice daily) was about 1 percent. (See BioWorld Today, Nov. 26, 2003.)

The trials enrolled 336, 377 and 734 patients, respectively, who were unable to control their blood sugar on common oral therapies including metformin, sulfonylurea or a combination of both.

The deal between Amylin and Lilly to take exenatide (once called AC2993) to market was signed in September 2002 and valued at a potential $435 million for Amylin. Amylin received a $110 million up-front payment, including Lilly's purchase of 1.6 million shares of Amylin stock worth about $30 million. So far, Lilly has paid out about $40 million in milestones.

Meanwhile, Amylin continues to work with the FDA to get Symlin (pramlintide acetate), a treatment for people with Type I and Type II diabetes, approved. Most recently, the FDA indicated that it wanted more data on Symlin before it would clear the drug. (See BioWorld Today, Dec. 19, 2003.)

Amylin believes it satisfied the request six months prior to the Prescription Drug User Fee Act in December by submitting data from a dose-titration study of about 300 patients and four small pharmacology studies. (See BioWorld Today, June 18, 2003.)

Further in its past, Symlin was rejected by an FDA advisory committee three years ago, though the agency later issued an approvable letter asking for another clinical trial. (See BioWorld Today, July 27, 2001, and Oct. 15, 2001.)

Amylin's stock (NASDAQ:AMLN) moved up 10 cents Monday to close at $20.10.

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