FDA will not likely complete its review of Amylin/Lilly's sNDA for the use of Byetta (exenatide) as monotherapy by the end of the year as previously forecast, the firms announced Dec. 8.

The partners are seeking to expand the indications for Byetta as a standalone drug for patients with type 2 diabetes who are not achieving acceptable blood sugar control. The glucagon-like peptide-1 analogue is currently approved as an adjunctive therapy for patients taking metformin, a sulfonylurea or a thiazolidinedione.

It's unclear whether the FDA delay stems from concerns over an increased risk of pancreatitis associated with Byetta or simply from the agency's ongoing regulatory review backlog. In addition to reviewing the monotherapy indication, FDA is also evaluating new safety language for Byetta's prescribing information.

In a statement, Amylin noted, "Our discussions with the FDA continue to progress, and we remain confident in the strength of our regulatory submission." The agency has not requested any additional studies, Amylin added.

A delay into 2009 puts FDA action on Byetta well behind the application's third quarter '08 PDUFA date. But this year, FDA has failed to issue timely approvability decisions on more than a dozen drugs and biologics, so a delay does not necessarily signal a negative outcome.

At the same time, Byetta is the subject of an ongoing safety concern, pancreatitis, an association that emerged earlier this year and has since cast an unwelcome shadow over the drug. FDA alerted health care providers to new cases of pancreatitis, including two fatal cases, in patients taking Byetta in August, an announcement that sent Amylin's shares tumbling (¹ Also see "Byetta Safety Concerns Could Set Roadblocks Ahead For New GLP-1s" - Pink Sheet, 21 August, 2008.).

Approval of the monotherapy indication with updated labeling would provide some guidance on FDA's thinking on the pancreatitis safety issue.

Investors are concerned over what a link between pancreatitis and Byetta could mean for new GLP-1s in development, particularly Amylin/Lilly's long-acting form of exenatide, Byetta LAR. In November, Amylin revealed that its first half 2009 filing target for Byetta LAR would potentially be set back following discussions with FDA (² Also see "Amylin Speculation Intensifies: Byetta LAR May Be Delayed" - Pink Sheet, 4 November, 2008.).

A delay could give rival Novo Nordisk more time to establish Victoza (liraglutide), its once-daily GLP-1, in the market should it be approved. The drug maker filed an NDA for Victoza in May, but an FDA decision isn't expected until after the agency's Endocrinologic and Metabolic Drugs Advisory Committee meets to discuss the application. That meeting, originally scheduled for March 2, was recently postponed one month until April 2 or 3.

Amylin's stock has continued to be battered on Wall Street. The share price has fallen by more than 75 percent since the Aug. 18 pancreatitis alert, leading the company to announce in November a cost savings program and elimination of 340 employees. The stock ended Dec. 8 at 8.76, up 5 percent from its close the day prior.

-Jessica Merrill (j.merrill@elsevier.com)

FDA Review Of Byetta Monotherapy Heads Into 2009

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