Washington Editor

Nearly two years after an FDA advisory panel rejected its application for use of Symlin as a treatment for glucose control in diabetics, Amylin Pharmaceuticals Inc. has put the finishing touches on an amendment and shipped it off to the FDA.

The San Diego-based company expects the FDA to take action on the application in six months, in accordance with the Prescription Drug User Fee Act (federal law requires the agency to act within a certain time period.)

Meanwhile, Amylin said it intends to offer $150 million of convertible senior notes for sale in a private placement. Proceeds will be used for activities surrounding Symlin, general corporate purposes and to help repay debt to former Symlin partner, New Brunswick, N.J.-based Johnson & Johnson.

Symlin (pramlintide acetate) is an analogue of human amylin, a hormone secreted with insulin by the beta cells in the pancreas. Specifically, Amylin is seeking FDA approval for use of Symlin as an adjunctive therapy to insulin for the treatment of Type I or Type II diabetics who use insulin.

Symlin is no stranger to the FDA. After its Endocrinologic and Metabolic Drugs Advisory Committee voted against recommending marketing clearance for Symlin, the FDA turned around and issued an approvable letter on the application. (See BioWorld Today, Oct. 15, 2001, and July 27, 2001.)

However, before the FDA would give Amylin the go-ahead to sell the drug, the agency wanted to see a few more tests.

"We went into discussions with the FDA and came up with five additional studies, four were very small pharmacology studies and the fifth was a more significant dose-titration study that we started in the spring of 2002 and completed early this year," Mark Foletta, Amylin's chief financial officer, told BioWorld Today.

The FDA and panel raised concerns about long-term studies of Symlin in which increased incidences of hypoglycemia or low blood sugar were noted. Thus, Amylin agreed to a dose-titration study in Type I patients.

"We introduced Symlin gradually in the first 30 days and we backed off the insulin at the outset of the study," Foletta said. "When Symlin was at the final dose, we allowed patients to adjust their insulin to get the best control."

In the first 30 days, 75 percent of the 300 patients in the study progressed to the highest recommended dose of 60 micrograms three times a day. "The incidents of hypoglycemia that they experienced were no different than placebo and in line with what long-term diabetes studies generally show," Foletta said.

Furthermore, he said 25 percent of patients who didn't progress beyond the lowest dose of 30 micrograms experienced lower hypoglycemia than patients in the control trials, which were reviewed by the FDA and led to the titration study. Most of those patients stayed on the drug and experienced efficacy benefits such as controlling blood sugar and weight control.

Amylin owns 100 percent of Symlin and expects to launch it on its own in the U.S. The company will market Symlin with the same sales force (45 people) it established to co-promote Indianapolis-based Eli Lilly & Co.'s Humatrope, a growth hormone deficiency product.

Amylin's former partner, Johnson & Johnson, pulled out of the deal 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. Johnson & Johnson invested about $175 million in the deal. (See BioWorld Today, Aug. 9, 1997, and March 3, 1998.)

The company withdrew its European Union application last October after getting signals that the regulators didn't have enough information and were not ready to make a decision. Foletta said the company plans to refile the application, although when that might happen has not been established. (See BioWorld Today, Oct. 25, 2002.)

Final terms on the $150 million in convertible senior notes were not available at press time. Foletta estimated that the coupon range would be 1.25 percent to 1.75 percent and the conversion premium would be in the 40 percent to 45 percent range.

It is expected that the notes would be due in 2008.

Amylin's stock (NASDAQ:AMLN) fell $1.23 Tuesday to close at $24.47.