Amylin Pharmaceuticals Inc. and partner Eli Lilly and Co. filed a new drug application seeking approval of exenatide as a treatment for Type II diabetes.
Exenatide (synthetic exendin-4), an incretin mimetic, demonstrated reductions in blood sugar and improvements in markers of beta-cell function in clinical trials. Also, on average, the trials ended with statistically significant reductions in weight, with improved glucose control, an unusual achievement in diabetes treatment, Eric Shearin, spokesman for San Diego-based Amylin, told BioWorld Today.
The candidate is a 39-amino-acid peptide in-licensed by Amylin from an individual researcher, who worked on it at an early development stage.
Shearin said the company is not sure whether the FDA will evaluate the application under priority-review guidelines. Applications in that category usually are reviewed within six months.
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. Data on an additional 400 patients also are part of the NDA.
Other data demonstrated improvements in beta-cell function, as measured by HOMA-B and proinsulin-to-insulin ratios, and the restoration of first-phase insulin response, the company said.
The package includes 52-week open-label data from the extensions of the "three amigos" and from an additional open-label study. Reductions in A1C were sustained through 52 weeks of treatment with average reductions of about 1.1 percent.
Like patients in the pivotal studies, participants in the open-label studies experienced reductions in weight, which was sustained through 52 weeks of treatment with average loss about eight pounds.
Amylin and Lilly, of Indianapolis, in September 2002 entered a deal potentially worth $435 million (for Amylin) to co-develop exenatide (then called AC2993). Amylin received a $110 million up-front payment that included Lilly's purchase of 1.6 million shares of Amylin common stock for about $30 million.
Shearin said the firms have not publicly released the milestone schedule, but he confirmed that filing the NDA does not trigger a payment.
The remainder of the deal includes $85 million in potential development milestones and about $130 million in commercialization milestones.
In another part of the Lilly agreement, Amylin is developing a long-acting-release formulation of exenatide, currently in Phase II trials.
Amylin's stock (NASDAQ:AMLN) was up 60 cents Wednesday to close at $22.80.