One big story from last week was the FDA advisory panel's "No" decision on Qnexa, the drug-combo obesity therapy developed by Vivus (VVUS). This is the one that's a combination of phentermine and topiramate, both of which have been around for a long time. And clinical trials showed that patients could indeed lose weight on the drug (with the required diet and exercise) - but also raised a lot of questions about safety.
And it's safety that's going to always be a worry with any obesity drug, even once you get past the (rather large) hurdle of showing efficacy. That's what took the Fen-Phen combination off the market, and what torpedoed Acomplia (rimonabant) and the other CB-1 compounds before they'd even been property launched. The FDA panel basically agreed that Qnexa helps with weight loss, but couldn't decide how bad the side effects might be in a wider patient population, and whether they'd be worth it:
But the drug has side effects, both known and theoretical. It may cause birth defects, it may increase suicide risk, it can cause a condition called metabolic acidosis that speeds bone loss, it increases risk of kidney stones, and may have other serious effects.
"It is difficult if not impossible to weigh these issues as the clinical trials went on only for a year, and patients will use this drug for lifetime," (panel chair Kenneth) Burman said. "It is impossible to extrapolate the trial data to the wider population."
That's a problem, all right, and it's not just Vivus that has to worry about it. When the potential number of patients is so large, well, any nasty side effects that are out there will show up eventually. How do you balance all these factors? Is it possible at all? As that WebMD article correctly points out, a new obesity drug will come on the market with all kinds of labeling about how it's only for people over some nasty BMI number, the morbidly obese, people with other life-threatening complications, and so on. But that's not how it's going to be prescribed. Not after a little while. Not with all the pent-up demand for an obesity drug.
Although that's probably the worst situation, this problem isn't confined to obesity therapies - any other drug that requires long-term dosing has this hanging over it (think diabetes, for one prominent example). That brings up the question that anyone looking over clinical trial data inevitably has to face: how much are the trials telling us about the real world? After all, the only way to be sure about how a drug will perform in millions of people for ten years is to dose millions of people for ten years. No one's going to want to pay for any drugs that have been through that sort of testing, I can tell you, so that puts us right where we are today, making judgment calls based on the best numbers we can get.
The FDA itself still has that call to make on Qnexa, and they could still approve it with all kinds of restrictive labeling and follow-up requirements. What about the other obesity compound coming along, then? A lot of people are watching Arena's (ARNA) lorcaserin (which I wrote about negatively here and followed up on here). Arena's stock seems to have climbed on the bad news for Vivus, but I have to say that I think that's fairly stupid. Lorcaserin may well show a friendlier side-effect profile than Qnexa, but if the FDA is going to play this tight, they could just let no one through at all - or send everyone back to the clinic for bankrupting.
As the first 5-HT2C compound to make it through, lorcaserin still worries me. A lot of people have tried that area out and failed, for one thing. And being first-to-market with a new CNS mechanism, in an area where huge masses of people are waiting to try out your drug. . .well, I don't see how you can not be nervous. I said the same thing about rimonabant, for the same reasons, and I haven't changed my opinion.
Disclosure: Since I got a lot of mail the last time I wrote about Arena, I should mention again that I have no position in the stock - or in any of the other companies in this space. But I could change my mind about that. If Arena runs up in advance of their FDA advisory panel in the absence of any new information, I'd consider going short (with money I could afford to lose). If I do that, I'll say so immediately.