Associate

Amylin Pharmaceuticals Inc. and partner Eli Lilly and Co. released partial results from their first of three exenatide Phase III trials in Type II diabetes, disclosing enough information to show the product hit its primary endpoint and to raise Amylin's stock.

The drug produced statistically significant, dose-dependent reductions in the primary glucose control endpoint in a seven-month trial involving Type II diabetes patients who failed to achieve target blood glucose levels with metformin alone. However, the company did not release hard data on the trial, instead planning to do so when all three trials are analyzed. But that was enough to cheer Amylin followers.

"We know it demonstrated positive results in terms of reducing the HbA1C and also in reductions in body weight," said Russell Gilbertson, analyst with Roth Capital Partners LLC in Newport Beach, Calif. "That's why the stock is moving up so strongly today."

Amylin's stock (NASDAQ:AMLN) rose $1.46 Thursday to close at $22.71.

The average entry hemoglobin A1C (HbA1C) - a measure that reflects average glucose levels over the prior three- to four-month period - for patients entering the study was 8.2 percent. At study's end, 46 percent of patients who received the highest dose (10 micrograms twice daily) reduced their average glucose levels to the amount recommended by the American Diabetes Association: less than or equal to 7 percent. Subjects receiving the highest dose of exenatide ended the study with an average HbA1C of 7.3 percent.

Exenatide (synthetic exendin-4) is a 39-amino-acid peptide that is designed to exhibit several glucose-lowering actions. Trials have shown that exenatide lowers post-meal glucagon concentrations and slows gastric emptying, Amylin said. Preclinical data have shown that exenatide reduces food consumption and can lead to reduced body weight. Also, in patients with Type II diabetes, exenatide administration can lower blood glucose concentrations, resulting in a reduction of HbA1c levels.

The results are good news, certainly, for Amylin, but the trial is just one of three the company has under way to support a new drug application filing. The company is scheduled to report on those trials in the fourth quarter, at which point it also would expose the full data set from the first trial.

Amylin, of San Diego, signed with Lilly, of Indianapolis, in September to co-develop exenatide (then called AC2993) in a deal that saw Amylin receive $80 million up front and another $30 million through a Lilly purchase of Amylin shares at $18.69 per share. Including milestone payments, the total value of the deal could reach more than $435 million. (See BioWorld Today, Sept. 23, 2002.)

Gilbertson sees an exenatide NDA filing in the first half of next year.

"I think this drug has great potential," he told BioWorld Today. "We anticipate approval in 2004 for Symlin, and we think [exenatide] is ultimately going to be a much bigger drug than Symlin."

The company is awaiting word from the FDA on Symlin, a diabetes drug that is still on its long, twisting road to approval. In June, Amylin filed its new drug application amendment to the FDA and is expecting a response before the end of the year, based on Prescription Drug User Fee Act guidelines. (See BioWorld Today, June 18, 2002.)

The drug officially was in the FDA's hands as far back as late 2000, when Amylin asked for marketing approval as an adjunctive therapy to insulin for the treatment of Type I or Type II diabetes. That followed a series of late-stage clinical setbacks. In July 2001, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted against recommending it for approval, but months later the agency issued an approvable letter that called for additional tests. (See BioWorld Today, Dec. 8, 2000; July 27, 2001; and Oct. 15, 2001.)

In October, Amylin withdrew its European marketing application for the product after officials there said additional information might be required. The company is still working with European authorities. (See BioWorld Today, Oct. 25, 2002.)

"They'll refile [in Europe] at some point," Gilbertson said. "They haven't said when, but they'll do that."

In June, Amylin raised $150 million through a sale of convertible senior notes due 2008. The company has not yet released its second-quarter earnings report but is expected to do so Aug. 14. As of March 31, it had $264.4 million in cash, cash equivalents and short-term investments - add that to the notes offering and Amylin has, as Gilbertson said, "a lot of cash right now." (See BioWorld Today, June 18, 2003.)

How much exenatide could add to the company's pockets depends on when it is approved, he said, but he estimates in his model the product doing $300 million in sales in 2007. That's a ways off, but with Symlin on the cusp of approval and exenatide shaping up well, Gilberston likes Amylin.

"I think it is a well-managed company and, unlike a lot of biotech companies, they seem to hit on all cylinders," he said. "That's a testament to how well run the company is and to their potential in terms of downstream revenue."