Just what is going on at Celgene (NASDAQ:CELG)? They've had some odd recent setbacks (such as the failure of Mongersen), and another such acquisition, Ozanimod, had its filing recently rejected by the FDA. Several things about that incident were eyebrow-raisers - for one, it's rare for a large, established company to get an outright refusal-to-file notice. That's one reason why you have a regulatory affairs group, to keep that sort of thing from happening - and if you're really working with the agency during development, it doesn't. (A refusal-to-file, for those outside the business, means that the FDA isn't even going to bother reviewing your application for a new drug approval because an initial inspection determined that the NDA package you submitted was obviously lacking. In other words, it's a "Don't waste our time" response).
Then it came out (during a recent American Academy of Neurology meeting) that most (maybe all?) of the drug's activity is due to a metabolite. Now that certainly happens. The liver chain-saws most of the drugs that people take, and some of those chopped-down versions of the original structure are also active on the drug's target. (Unfortunately, some of them might be active on other targets, too, which is another thing you'd like to discover as early as possible). And that's just what was odd about this: how come the company didn't know about this active metabolite earlier? And why wasn't this issue fully addressed for the FDA?
