FDA Byetta Review for Expanded Use Delayed as Agency Reviews Warning Revisions

According to a statement released today by Amylin Pharmaceuticals and Eli Lilly, the FDA’s review of their application to allow use of Byetta as a stand-alone therapy for treatment of type 2 diabetes will be delayed, as the FDA is also reviewing other updates to the Byetta prescribing information and safety language, which could include new warnings about a possible risk of pancreatitis with Byetta.

Byetta (exenatide), which is jointly marketed by Amylin and Lilly, has been used by nearly 1 million people in the United States to help control blood sugar levels in type 2 diabetics. It is currently approved as an add-on therapy for people also using metformin, a sulfonylurea drug or a thiazolidinedione medication, such as Avandia or Actos.

The drug makers filed an application earlier this year for approval to market Byetta as a stand-alone diabetes treatment. While they indicate that the FDA has not requested additional studies for this application, the review will likely extend into 2009.

The companies indicate that in addition to reviewing the application for use of Byetta as a stand-alone therapy, the FDA is also reviewing other possible updates to the prescription information and warning label about possible Byetta side effects.

Following recent reports which associated the use of the drug with pancreatitis, there has been speculation that the FDA is considering a “black box” warning for Byetta, which is the strongest type of warning that can be placed on a prescription medication.

In October 2007, the FDA notified doctors that they have received reports of at least 30 cases of acute pancreatitis with Byetta users, leading to the addition of new language to the drug’s label about the possible association.

In August 2008, the FDA issued another alert to notify doctors about an additional 6 cases of severe pancreatitis among Byetta users, including two deaths. These reports involved cases of hemorrhagic pancreatitis, where massive erosion of blood vessels can lead to severe bleeding, and necrotizing pancreatitis, which involves tissue damage and can lead to multi-organ failure and death.

Following the August FDA safety alert, Lilly and Amylin held a conference call with investors and users, where they disclosed that they were aware of at least four other deaths among users of Byetta from pancreatitis. Although they have denied that there is any causation between Byetta and pancreatitis, the companies acknowledged that they were in talks with the FDA about stronger warnings about possible Byetta pancreatitis side effects.

Amylin, which is heavily reliant on Byetta sales, has suffered several setbacks this year, since concerns about Byetta pancreatitis risks emerged. Their stock price fell nearly 20% during the eight weeks after the August FDA alert, and they announced recently that they are cutting their work force by 25% following unexpectedly slumping sales.

Last month, it was also reported that the FDA rejected data submitted by the drug makers involving a longer-acting version of Byetta, which would only be administered once a week, as opposed to twice daily. Although there is no indication that this delay is connected to the potential pancreatitis risks, additional clinical trials may be required, which will likely delay their filing for this new version until late 2010 or early 2011, with approval and sales potentially not occurring until 2012.