Eli Lilly and Amylin Pharmaceuticals Inc. on Tuesday reported four new deaths in patients taking Byetta, even as the companies tried to shore up the safety profile of their popular diabetes medication.

The announcement comes a week after the Food and Drug Administration said two Byetta patients died of acute pancreatitis, sinking shares of both drugmakers. An executive from Eli Lilly said the FDA was aware of the additional deaths but did not announce them because they involved a milder form the pancreatitis. The condition can cause nausea, vomiting and abdominal pain.

“They were concentrating on the more severe forms of the condition, but we felt it was important to get this information out there,” Eli Lilly Medical Director James Malone told the Associated Press.

Malone stressed that all four patients had complicating medical conditions, which were likely the primary cause of death. In two instances, patients died after experiencing complications following gallbladder surgery, while another patient died after a relapse of leukemia. The company still has not gotten additional information on the fourth death.

Shares of Amylin fell $2.24, or 8.2 percent, to $25. Shares of Eli Lilly fell 52 cents to $46.50.

Since the FDA announcement, Eli Lilly shares have fallen over 3 percent, while shares of Amylin Pharmaceuticals have fallen nearly 20 percent. San Diego-based Amylin co-developed Byetta and makes about 80 percent of its revenue from the injectable drug. The drug accounted for about 3 percent of Lilly’s sales last year.

Prescriptions for the twice-daily treatment fell 2.1 percent last week, according to pharmaceutical data firm IMS Health.

Malone said that media coverage of the deaths with Byetta “tended to be a bit sensationalized.”

He noted there has been only one report of pancreatitis for every 3,000 patients taking the drug for one year.

While the company cannot rule out a connection between its drug and the pancreas problems, Malone said there have been reports of similar problems with rival medications.

“With all other diabetes medications we know there has been pancreatitis, and some of those people have died,” said Malone. “So it’s not a unique phenomenon with Byetta.” He added that diabetes patients are already three times more likely to develop pancreatitis compared with healthy patients.

The FDA said last week it would seek a stronger, more prominent warning for Byetta, but details of the new label are still in the works.

Malone also tried to ease concerns about the timeline for company’s long-acting version of Byetta _ which is formulated for use once a week, instead of twice a day. He said the companies still hope to bring the drug to market by mid-2009 and that there are no plans for additional studies, despite the FDA’s safety concerns.

Lilly and Amylin Pharmaceuticals split worldwide sales of Byetta, which grew over 50 percent to $650 million last year. Wall Street continues to maintain a positive outlook for the drug and the next-generation formula.

Leerink Swann & Co. analyst Jonas V. Alaenas, reaffirmed an “Outperform” rating on Amylin Monday, calling the pancreatitis concerns “overblown.” Last week, Goldman Sachs analyst Meg Malloy reaffirmed a “Buy” rating with a similar comment.

Approved in 2005, Byetta was the first in a new class of diabetes medications that have shown improved ability to control blood sugar levels. The drug is expected to face competing products as soon as next year.

In June, Danish drugmaker Novo Nordisk reported data showing its experimental drug liraglutide was more effective than Byetta at controlling blood sugar levels. Swiss firm Roche is also working on its own next-generation diabetes medication.

Considering competition from Novo Nordisk and others, Robert Hazlett expects long-acting Byetta to make $100 million in sales during its first year on the market, compared with earlier analyst estimates of up to $700 million.

Lower revenues from the drug would also impact biotech company Alkermes Inc., which helped develop the longer-acting formula and is slated to receive royalties from its sales.

Eli Lilly and Amylin Pharmaceuticals report four new deaths in patients taking the diabetes medication Byetta.

An executive from Indianapolis-based Eli Lilly says the FDA is aware of the additional deaths but did not announce them because they involved a milder form the pancreatitis. The condition can cause nausea, vomiting and abdominal pain.

Lilly medical director James Malone says all four patients had complicating medical conditions, ranging from leukemia to gallstones, which were likely the primary cause of death.

Malone says media coverage of the deaths with Byetta “tended to be a bit sensationalized.”

Copyright 2008 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Last week, the FDA said it had received reports of six new cases of pancreatitis – including two deaths – associated with the diabetes drug Byetta. Today, Amylin and Eli Lilly said that they had reported four additional deaths to the agency as well, which the FDA hasn’t yet made public.

The companies, which co-market the drug, chose to disclose the additional information in order to “provide context” about each of the cases, because the medical community appeared confused by the information last week, Amylin President and Chief Executive Daniel Bradbury told the Health Blog.

Another reason might be to reassure investors. Byetta, co-marketed by the companies, already has a label reflecting its association with severe inflammation of the pancreas. But the FDA says it’s working on a stronger label for the drug that includes forms of pancreatitis that involve bleeding and cell death. Both companies’ stock dipped following the news last week, though Amylin’s was particularly hard hit, plunging as much as 22% since the FDA announcement before recovering somewhat.

In the four cases brought forward by the companies today, it’s not clear whether the patients were taking Byetta at the time of deaths. And the deaths are “not directly attributable to pancreatitis in any way”, Orville Kolterman, Amylin’s senior vice president of R&D, told us. For instance, one patient appeared to die from a relapse of leukemia two months after having pancreatitis. Also, patients with Type II diabetes have a greater risk of pancreatitis than healthy people to begin with, said Kolterman.

Analysts say the bigger picture issue is whether these safety concerns might affect the long-acting version of the medicine the companies are currently developing. The question “is whether the FDA, from a regulatory standpoint, will require longer term study of” the long-acting version, Barbara Ryan of Deutsche Bank told the Health Blog. “Rather than a short half-life, you’re going to have a longer term product. So if you get in trouble, it’s [in the body] for a longer period of time.”