Washington Editor

FDA approvals are becoming routine for Amylin Pharmaceuticals Inc., which just received the agency's blessing for the second time in less than two months.

On Friday, the FDA approved a new diabetes drug, Byetta (exenatide), which was developed in partnership with Eli Lilly and Co. That follows on the heels of the approval of Symlin (pramlintide acetate), another diabetes drug born out of San Diego-based Amylin's research efforts. (See BioWorld Today, March 18, 2005.)

"We are extraordinarily excited today," Amylin President and CEO Ginger Graham said amid a round of cheers during a conference call. "All of us here, across the company, are celebrating the approval of a product that we believe can make a huge difference."

A twice-daily injectable product, Byetta is indicated as an adjunctive therapy to improve blood sugar control in Type II diabetics who have not achieved adequate control on two common oral diabetes medications, metformin or sulfonylurea, or a combination of the two. Its launch, expected in the next month, will trigger a $30 million milestone payment to Amylin, which gained the latest approval more easily than Symlin.

"We've been working with the same [FDA] division on these two first-in-class products," Eric Shearin, Amylin's senior manager of corporate communications, told BioWorld Today.

Byetta was approved on the basis of a new drug application that included pivotal data showing that the drug met all primary glucose-control endpoints, including sustained 52-week reductions in hemoglobin A1c levels that averaged about 1.1 percent. (See BioWorld Today, July 1, 2004.)

"In spite of frequent changes in therapy, about 60 percent of diabetes patients do not achieve glucose control targets recommended by the American Diabetes Association," said Orville Kolterman, Amylin's senior vice president of clinical affairs. "Thus, new therapies that work through different mechanisms of action are needed."

Initially isolated from salivary secretions from the Gila monster, Byetta improves blood sugar control by lowering both post-meal and fasting glucose levels, leading to better long-term control as measured by hemoglobin A1C. Several mechanisms are at play, including the stimulation of insulin secretion only when blood sugar is high and by restoring the first-phase insulin response, a function of the insulin-producing cells in the pancreas that is lost in patients with Type II diabetes. Also, most patients in long-term studies lost weight.

"These multiple actions combined," Kolterman said, "contributed to the clinical effects observed in the Byetta Phase III program. The clinical portion of the label includes data from the three 30-week pivotal trials in over 1,400 patients."

The drug, the first in a new class of medicines called incretin mimetics, will soon be available to pharmacies as the partners begin to tap a large and growing market. Neither company forecast potential sales goals, but said that about 90 percent to 95 percent of America's 18 million diabetics have Type II diabetes. Byetta will be available in both a 5-microgram and a 10-microgram prefilled pen-injector device.

Marketing will be handled on an equal co-promotion basis by Lilly and Amylin, which has developed a sales force of more than 300 people. In fact, earlier this year Amylin raised $176 million through a public offering to expand its commercialization capabilities with an eye toward both approvals. Sales of Symlin, indicated for Type I and late-stage Type II diabetics, already are under way. (See BioWorld Today, Jan. 24, 2005.)

"No company of any size, that I'm aware of, has ever accomplished this in one year and certainly not in two consecutive months," Graham said. "It is a critical component of our mission to provide innovative medicine to people with diabetes and other metabolic disorders."

Amylin and Lilly also expect to seek a label expansion for Byetta, as the FDA said the drug is approvable as monotherapy for Type II diabetics. Any additional data submitted to support a monotherapy indication are expected to receive a six-month review. The partners also made Phase IV commitments that include a small pediatric trial and a drug-interaction study with oral contraceptives.

The partnership has a potential worth of $435 million for Amylin, which received a $110 million up-front payment from Indianapolis-based Lilly at the outset. In another part of the collaboration, Amylin is developing a long-acting, once-weekly formulation of exenatide through a program in Phase II.

Beyond its two approved diabetes drugs, the company's portfolio includes four clinical development programs: two focused on diabetes, including one that employs the same active ingredient as Symlin, as well as two directed toward cardiovascular indications.

On Friday, shares in Amylin (NASDAQ:AMLN) lost $1.18 cents to close at $17.