FDA’s Woodcock Talks Obesity Drug Safety

Janet Woodcock, head of FDA's drugs center, had a few things to say about obesity drugs at Monday's Reuters Health Summit in New York. Some of her comments weren't surprising. But some of them might offer a sliver of hope to companies hoping to succeed where Arena Pharmaceuticals, Orexigen Therapeutics, and Vivus have so far failed-- in bringing a new diet pill to market. From a Reuters story, which was brought to my attention via Twitter by David Pittman, a former C&EN contributor now working at FDA News (Thanks for the tip, David!):
For diet drugs, Woodcock said companies might find success by showing benefits beyond weight loss such as a decrease in blood pressure or reversal of diabetes. "Those would be benefits you might accept more risk for," Woodcock said. The FDA recently rejected diet drugs with various safety issues from Arena Pharmaceuticals Inc (ARNA.O), Orexigen Therapeutics Inc (OREX.O) and Vivus Inc (VVUS.O). The agency also asked Abbott Laboratories Inc (ABT.N) to withdraw its diet medicine, Meridia, from the market due to heart risks and the company agreed.
It's not surprising to hear Woodcock say that a potential weight loss pill's risks must be balanced by clear benefits. Having positive effects on things that can be consequences of obesity, such as blood pressure and blood sugar control, is one way of achieving that balance. Another way is to show FDA that your risks aren't all that risky. On that topic, I was intrigued to read Arena's announcementthat it isn't conducting the 12-month study FDA asked for to evaluate how its obesity drug candidate lorcaserin caused tumors in rats, and is conducting a three-month study instead. Now, what really caught my eye in Woodcock's statements was this gem:
Woodcock said the FDA would not mandate additional benefits beyond weight loss diet drugs with relatively low risks. "There are some weight loss drugs out there that don't have much serious risk and cause modest weight loss and we think that's important for people," she said.
Woodcock seems to be talking about drugs already on the market, but I'm not entirely sure. (Does anyone have a transcript of this talk?) This is the kind of sentence that makes me scratch my head and ask- just where does FDA's safety bar lie? We know that the experimental pills from Arena, Orexigen, and Vivus haven't cleared it. After that trio of rejections, stimulating discussions popped up on Matthew Herper's blog at Forbes and elsewhere about whether obesity drugs are dead. But maybe the key to a weight-loss drug, as opposed to a diabetes drug that happens to have the added benefit of weight loss, will come from developing candidates that work completely differently from what's been seen so far. Olivier Boss, chief scientific officer for Energesis Pharmaceuticals and Twitterer extraordinaire, alluded to this when he commented on Herper's blog. Here's what Boss said:
I agree that it is likely that it will be years before a new anti-obesity drug gets on the market. However, the obesity field (for drug development) is by no means dead (whether diabetes is used as first indication or not). All anti-obesity drugs/candidates developed to date are “diet drugs” or “appetite suppressants” acting on CNS targets (except Xenical, an anti-fat absorption drug). This was the FIRST GENERATION obesity drugs (following the CNS-targeted amphetamines of the 1970s). Knowledge of regulation of energy balance, food intake and energy expenditure (especially thermogenesis) has improved tremendously in the last decade, and new approaches (non-CNS based) are being developed by a few companies. It is still early stage, for sure, but these new strategies are completely novel, and some (like brown fat recruitment) have been well established in many animal models.
So how much risk would weight loss drugs that work outside of the nervous system have? We don't know yet. But companies like Energesis and Zafgen are set on finding out.

Author: Carmen Drahl

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