Has Forest Found a Successful NDA Path?

Is there a way out of the woods for pharma companies hoping to win approval from the Food & Drug Administration for products for broad primary care populations?

FDA’s imminent decision on Forest Lab’s pending new drug application for the beta blocker nebivolol for hypertension may show one way.

Because of a two-and-half year delay, the product is coming up for a final decision at one of the worst times for applications aimed to provide treatment for an indication which is already served by a broad array of existing products.

FDA’s senior staff has been telling astonished sponsors that the new de facto approval criteria being imposed by FDA reviewers require convincing arguments of comparative safety or efficacy advantages for primary care drugs. (You can read more about that in “Straight Talk from FDA” published by The RPM Report in November.)

By serendipity, Forest may have the type of relatively familiar and market-proven product (from outside the US) that can satisfy the new climate.

The delay in the NDA may actually have helped the cause for the product by taking some of the pressure off the NDA review schedule for FDA. The product has a well-defined tolerability profile and an extensive marketing record outside the US.

Forest is facing an approval decision at the end of 2007 because Forest’s partner on the product (Mylan Labs) received an approvable letter in May 2004 when it was developing the product by itself. Mylan quickly put nebivolol up for out-license after the setback. Forest bought rights to the product in January 2006.

Mylan submitted an update to the original application with answers to FDA’s questions on preclinical data in early May of this year. Nebivolol falls into a familiar class. It is a third-generation beta blocker where two other third-generation products have been on the market for many years. The broader class of all beta blockers has been around for forty years. Nebivolol itself has been marketed in Europe for over ten years.

Throughout its development phase in the US, Forest and Mylan have stressed the product’s improved side effect profile. In a summary of the first published data from a US clinical trial in September of this year, Forest reports that the incidence of adverse events “commonly associated with traditional beta blocker use, including fatigue (3.6% vs. 2.5% with placebo), erectile dysfunction (0.2%), and depression (0.2%) was low. Moreover, nebivolol was not associated with adverse changes in blood glucose values.”

Mylan and Forest suggest a potential added benefit as a vasodilator based on an effect on nitric oxide. One of the researchers who has been writing about the product frequently during clinical development, George Bakris, MD, Rush University Medical Center, wrote in a managed care journal recently “the risk for diabetes is lower, the metabolic effects are lower, and people with diabetes who have clear NO dysfunction may have particular benefits from this agent.”

Forest is obviously eagerly awaiting this launch and says it has committed $80 million in 2008 to fund the marketing support. Is FDA ready to take the risk of approval on even an old product? If not, 2007 already a memorably bad year for drug approvals will go down as even a worse nightmare for the industry.