Why NicOx Ran Into an FDA Stone Wall With Its "Safer" Arthritis Drug

Last Updated May 13, 2010 9:37 AM EDT

improving Vioxx and AspirinWhen is positive Phase III data not enough to sway an FDA advisory panel? When you're French pharma firm NicOx (COX.PA).

NicOx's drug naproxcinod is designed to be a safer treatment for arthritis pain. Safer than, say, Merck's (MRK) Vioxx (rofecoxib) or Pfizer's (PFE) Bextra (valdecoxib), both of which were pulled from the market amid an uproar about heart attack and stroke risks. In fact, the FDA subsequently required all NSAIDs (non-steroidal anti-inflammatory drugs) -- even over the counter versions like aspirin and Aleve -- to carry warnings about cardiovascular risks.

Naproxcinod combines the NSAID naproxen with nitric oxide, which should theoretically dilate blood vessels and reduce high blood pressure. NicOx was also aiming to reduce gastrointestinal side effects like ulcers.

NicOx completed clinical trials in more than 6,700 patients, and three Phase III trials met their endpoints of improving pain relief compared to placebo. FDA briefing documents released earlier this week and an expert panel review yesterday seemed convinced on that point.

The problem is, that's not enough. That just puts naproxcinod on even footing with the myriad other NSAIDs on the market, many of which are cheap generics or over-the-counter medicines. NicOx needs naproxcinod's label to say the drug is safer than all the rest, and neither the FDA nor its advisors seemed convinced on that point.

The FDA was so harsh on NicOx's claim of better gastrointestinal tolerability and fewer ulcers that the company already said yesterday it would pull that language out of its proposed label. The blood pressure lowering claim is the more important one, but the agency said those effects were seen only at the drug's peak and weren't consistent enough in the longer term. The FDA also questioned whether or not blood pressure in older patients dipped too low at the peak, and they cited problems with NicOx's analysis showing that naproxcinod is not inferior to naproxen.

The advisory panel voted 16-to-1 against approval. According to a BioWorld Today article, one panelist liked the concept of the drug, but in the words of another panelist:

I'm struggling with why I would give this drug to my patients instead of naproxen.
Which raises an interesting question for the FDA's July decision on naproxcinod's approvability. If the drug seems to be as safe and effective as other NSAIDs, do you reject it because it isn't clearly better than what's already out there? Or do you approve it without the fancy-schmancy blood pressure and ulcer claims and let the market dynamics sort out whether it succeeds or fails?

NSAID warning photo by Flickr user Rob!, CC.

  • Trista Morrison

    Trista Morrison is a staff writer at BioWorld Today, a daily newspaper that