Washington Editor

Amylin Pharmaceuticals Inc. believes it possesses adequate clinical data on the diabetes drug Symlin to satisfy questions raised by the FDA in a second approvable letter issued this week.

The company's stock (NASDAQ:AMLN) dipped $1.55 Thursday to close at $21.88 on news that the FDA wants more data before it will approve Symlin.

That is yet another setback in Symlin's journey to the market. Symlin (pramlintide acetate), Amylin's lead candidate, is proposed for the treatment of people with Type I and Type II (insulin-dependent) diabetes.

Despite rejection by the FDA's Endocrinologic and Metabolic Drugs Advisory committee more than two years ago, the agency in October 2001 issued an approvable letter for Symlin if the company would conduct another clinical trial. (See BioWorld Today, July 27, 2001, and Oct. 15, 2001.)

Another trial, according to Eric Shearin, Amylin's senior manager of corporate communications, amounted to a dose-titration study in about 300 patients and four small pharmacology studies, all of which were completed and submitted to the government in June. (See BioWorld Today, June 18, 2003.)

Shearin said the second approvable letter is in response to that data. The company's next step, though, is not clear.

"We are still trying to discern exactly what this means," he said. "At this time, based on their request, we believe the data [the FDA wants] exists from open-label studies conducted since the amendment" was submitted in June.

Shearin was speaking of an open-label extension of the dose-titration study and another large open-label study initiated earlier this year. In its latest request, the FDA asked for clinical data to identify a patient population and method of use for Symlin in which there is no increased risk of significant hypoglycemia or in which there is an additional benefit that counterbalances any potential for increases in episodes of hypoglycemia, the company said.

Amylin has requested a discussion with the FDA regarding specific requirements for approval. At this point, Shearin said, it is too early to estimate a timeline as to when the discussion will take place.

Symlin is an analogue of human amylin, a hormone secreted with insulin by the beta cells in the pancreas. Amylin proposes injecting diabetes patients with Symlin three times a day in conjunction with insulin. The product controls blood sugar and weight gain, studies have indicated.

San Diego-based Amylin owns 100 percent of Symlin and anticipates launching it on its own in the U.S. Former partner New Brunswick, N.J.-based Johnson & Johnson pulled out of the collaboration in 1997 when a Phase III trial in Type II diabetes failed to show lower glucose on an intent-to-treat basis after 12 months. J&J had invested about $175 million in the deal. (See BioWorld Today, Aug. 9, 1997, and March 3, 1998.)

While the Symlin application is currently pending in Switzerland, Amylin has yet to re-file in Europe following its decision to withdraw the application last October after getting signals that it was lacking in certain information. (See BioWorld Today, Oct. 25, 2002.)

Shearin said the company currently is evaluating the best way to reapply in Europe. On approval overseas, Amylin might consider seeking a commercialization partner.

Amylin recently filed a $300 million mixed-shelf registration statement that would allow it to sell various securities, such as common and preferred stock, debt and warrants in the future. Among the purposes, Amylin is looking to raise money to commercialize Symlin and to help advance another product, called exenatide.

Amylin and partner Eli Lilly & Co., of Indianapolis, are developing exenatide, a first-in-class candidate for Type II diabetes. Exenatide (synthetic exendin-4) is a 39-amino-acid peptide that is designed to exhibit several glucose-lowering actions.

The partners have successfully completed three pivotal Phase III trials and expect to submit a new drug application in mid-2004. Amylin said Thursday that Lilly agreed to pay the first development milestone in their collaboration, which will bring $35 million to Amylin.

Financially, for the quarter ended Sept. 30, Amylin had about $289 million in cash. Its estimated burn rate for 2003 is $140 million to $150 million and the company expects to finish the year with $260 million, which assumes certain payments from Lilly.