FDA Rejects New Byetta Formula, Questions Health Risks and Manufacturing

The FDA has denied approval for a once-weekly version of Eli Lilly’s and Amylin Pharmaceuticals’ diabetes drug Byetta, saying that the agency needs answers to certain questions about the drug makers’ manufacturing processes and how it intends to mitigate Byetta health risks to users. 

Amylin announced the FDA’s rejection of their new Byetta formulation on Monday. The proposed drug, Bydureon, would allow users to take one dose a week to regulate their diabetes, as opposed to Byetta, which is a twice-daily injection. Bydureon has also been commonly referred to as Byetta LAR.

While the FDA has not asked for lengthy additional clinical trials, which would delay release of the drug significantly, Amylin officials say the agency sent the company a letter indicating that they need to provide finalized information for what will be on the new drug’s label, a risk evaluation and mitigation strategy (REMS) for reducing the health risks to users, and clarification on the manufacturing processes for the medication.

Last week the FDA released an inspection report about problems at the Byetta manufacturing plant in Ohio, which cited a number of quality control and staff training issues. Among problems found at the plant, FDA inspectors said that raw materials used to make Byetta were not properly inspected coming into the plant, and workers in a variety of positions have not been properly trained to ensure quality control.

Byetta (exenatide) is a type 2 diabetes drug that is manufactured and distributed jointly by Amylin and Eli Lilly & Co. The drug is used to control blood sugar levels and is part of a class of medications known as incretin mimetics, which imitate natural hormones that lower blood glucose levels.

In November, the FDA issued a warning indicating that they had received at least 78 post-marketing reports which raised concerns about Byetta kidney problems, with 62 of those reports involving users experiencing kidney failure. The alert followed FDA warnings issued in October 2007 and August 2008 of reports involving cases of pancreatitis with Byetta, including severe reports of hemorrhagic pancreatitis and necrotizing pancreatitis, which can be fatal.

In cases where a drug that is deemed important to patients also causes serious health problems, the FDA can require a REMS report that details how the drug maker intends to provide the drug in a way that reduces risk to patients as much as possible.

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