Byetta Pancreatitis Risk Needs Further Studies: FDA

The FDA has required the makers of the diabetes drug Byetta to conduct additional studies to clarify the risk of pancreatitis from side effects of their medication.

Byetta (exenatide) is a type 2 diabetes drug that is used to control blood sugar levels. It is part of a class of medications known as incretin mimetics, which imitate natural hormones that lower blood glucose levels.

The FDA recently expanded the approval of Byetta for use as a standalone treatment, without use of other diabetes drugs. On October 30, Eli Lilly & Co. and Amylin Pharmaceuticals, Inc., which jointly market the drug, announced the new approval and indicated that warnings about the risk of pancreatitis from Byetta would be added to the label. However, they did not disclose that additional studies were being required to further examine the pancreatitis risk.

Citigroup analyst Yaron Werber informed investors last week that the FDA is also requiring additional post-marketing studies into the potential Byetta pancreatitis side effects and a Risk Evaluation and Mitigation Stategy (REMS), which would be used to ensure that the drug’s benefits outweigh the risks. The information was obtained from a copy of the FDA’s approval letter.

Concerns about the potential Byetta pancreatitis risk first surfaced in October 2007, when the FDA issued an alert indicating that the drug had been linked to at least 30 reports of acute pancreatitis. In August 2008, the FDA notified doctors about six more cases of severe pancreatitis from Byetta, including two deaths. Following the FDA announcement, the drug makers disclosed that they were aware of at least four other pancreatitis deaths among Byetta users.

According to the FDA approval letter [PDF] expanding Byetta as a standalone therapy, the FDA identified “new safety information” that they have become aware of since the drug was originally approved in April 2005, including postmarketing reports of acute pancreatitis, hemorrhagic pancreatitis, necrotizing pancreatitis, renal failure and thyroid neoplasms associated with side effects of Byetta.

“After considering this new safety information, we have determined that postmarketing requirements are needed to assess the risk of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, and the risk of thyroid neoplasms, and that a REMS is necessary for Byetta (exenatide) to ensure that the benefits of the drug outweigh the risks of acute pancreatitis and acute renal failure,” the FDA states in the letter.

On November 2, the FDA announced that new warnings would be added to the drug about the potential Byetta kidney side effects, indicating that the agency has received at least 78 post-marketing reports of users who developed altered kidney function, including 62 reports of kidney failure. The new warnings indicated doctors should watch for signs of kidney problems from Byetta, especially when starting treatment or increasing dosage in patients with moderate pre-existing kidney function issues.

Amylin and Eli Lilly already face a number of Byetta lawsuits involving allegations that the drug makers failed to adequately warn about the risk of pancreatitis and kidney failure from the diabetes drug.