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NSAID GI Safety to Go Under FDA Advisory Panel's Endoscope


 

A Food and Drug Administration advisory committee is scheduled to discuss the criteria for a claim of preventing NSAID-triggered gastrointestinal complications at a Nov. 4 meeting.

The agency is continuing to refine its criteria for approving label claims that tout improved GI safety for NSAIDs.

At the meeting, the agency will ask its Gastrointestinal Drugs Advisory Committee to discuss whether endoscopically documented gastric ulcers are an adequate outcome measure to evaluate drugs that are intended to prevent such NSAID-triggered GI complications.

A recent trend in drug development is to combine NSAIDs with such drugs. For example, AstraZeneca’s Vimovo (naproxen/esomeprazole) was approved in April, with an indication of “relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID associated gastric ulcers.”

But the agency is scrutinizing such combination claims closely. In late 2008, while Vimovo, which was codeveloped with Pozen Inc., was still in phase III clinical trials, the FDA began reassessing end point requirements for NSAID/proton pump inhibitor products to address inconsistencies between the Gastroenterology Drugs Division and the Analgesics, Anesthetics, and Rheumatology Products Division.

This created a worrisome situation for Pozen, which had a special protocol assessment in place, a written agreement under which the FDA had agreed to allow the company to use gastric ulcer reduction as measured by endoscopy as a primary end point. The company hinted at the time that it would consider suing the agency to enforce the special protocol assessment.

Other products may still be on the hot seat. Currently under review is Horizon Pharma Inc.’s New Drug Application for Duexa (ibuprofen/famotidine), a fixed-dose tablet formulation of the NSAID and a high dose of the H2 antagonist to reduce the risk of development of upper gastrointestinal ulcers in patients with arthritis and pain.

In what may well be an ominous sign of things to come, the FDA’s “complete response” letter to NicOx Inc. for its naproxcinod called for the firm to do additional safety studies and demonstrate the clinical benefit it was claiming of prevention of gastropathy and elevated blood pressure triggered by the NSAID. This followed a negative vote by the FDA’s Drug Safety and Risk Management Committee and Arthritis Advisory Committee on May 12.

Elsevier Global Medical News and “The Pink Sheet” are published by Elsevier.