A failure of vigilance

Last evening (August 26, 2008), the manufacturer of Byetta (Amylin Pharmaceuticals, Inc., partnering with Eli Lilly) released information attempting to reassure patients, physicians, and investors that Byetta was safe, despite increasing evidence that may link the drug to a sometimes-fatal complication of diabetes called pancreatitis. In my opinion, they failed.

First, let me remind everyone that the possible association between Byetta and pancreatitis is not proven, and there definitely is an association between T2DM and pancreatitis. What's not yet understood is whether Byetta increases the risk of developing pancreatitis. Amylin and Lilly have announced that they "continue to pursue a comprehensive drug safety program that includes extensive internal and external review of individual cases, and clinical and epidemiologic studies."

A brief history of Byetta-associated pancreatitis follows.

The U.S. prescribing information for Byetta (also known as exenatide) includes  information about the possibility of developing pancreatitis. The present wording is in the PRECAUTIONS section of the label, and reads: "Postmarketing cases of acute pancreatitis have been reported in patients treated with BYETTA. Patients should be informed that persistent severe abdominal pain, which may be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. If pancreatitis is suspected, BYETTA and other potentially suspect drugs should be discontinued, confirmatory tests performed and appropriate treatment initiated. Resuming treatment with BYETTA is not recommended if pancreatitis is confirmed and an alternative etiology for the pancreatitis has not been identified."

In October 2007, the FDA announced that they had reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta, and that an association between Byetta and acute pancreatitis was suspected in some of these cases.

A week ago, on August 18, the FDA had stated there were two deaths from pancreatitis in patients taking Byetta:

Since issuing Information for Healthcare Professionals in October 2007, FDA has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Byetta is a medicine given by subcutaneous injection to help treat adults with type 2 diabetes. Of the 6 cases of hemorrhagic or necrotizing pancreatitis, all patients required hospitalization, two patients died and four patients were recovering at time of reporting.  Byetta was discontinued in all 6 cases.   

But now we're finding out that there were not 2 pancreatitis-associated deaths, but 6.

Apparently, the four newly-publicized deaths involved patients who had complicating medical conditions in addition to type 2 diabetes, ranging from leukemia to gallstones, which were likely the primary cause of death. According to the AP, Lilly's medical director, James Malone, said that the FDA was aware of these four additional deaths last week, but did not make them public because they involved a milder form of pancreatitis.