Lessons Learned About the Outlook for New Obesity Drug Approval

7/16/10

Yesterday’s FDA advisory committee meeting on Vivus’ weight loss pill proved to us, once again, how incredibly difficult it is to successfully develop and register new drugs for obesity. Mountain View, CA-based Vivus had a solid program supporting their drug—demonstrating that their combination product of phentermine and topirimate (Qnexa) is very effective and has a defined safety profile worthy of a regulatory approval. Phentermine is better known as the ‘phen’ in fen-phen, and topirimate is used for the treatment of epilepsy, migraine, and a significant amount of obesity off-label.

The good news is that the combination—tested by Vivus at three dose levels—was effective, showing a clear dose response that resulted in a median weight loss (at the high dose) of about 15 percent for patients who completed 56 weeks of treatment. That’s a serious amount of weight, considering that your average obese patients weigh around 220 pounds or more. Furthermore, the Vivus drug demonstrated some very impressive salutary effects on other endpoints that travel with obesity—including blood glucose, blood pressure, HDL and LDL cholesterol, sleep apnea, and inflammation markers.

There were some compelling speeches from patient advocates, too. I have to confess, I choked up a bit when one young and striking patient who had been transformed with tremendous weight loss during her trial experience on the Vivus drug tearfully pleaded to the panel to support approval, saying “We need help. I … need help.” She, like others who were quoted by Kelly L. Close, who edits a journal called diaTribe and spoke passionately for approval—view obesity as ‘a nightmare I cannot wake up from.”

It’s true—obesity is a lifelong struggle. She and the rest of us need to have good tools in the hands of our physicians to keep weight in check, just like we do for hypertension, high cholesterol, and other chronic diseases. It’s very touching stuff, and sobering too. Especially when you consider that 30 percent or more of U.S. adults are obese, and that the strategies being taken to stop the problem through diet and exercise are about as effective against established obesity as a sponge mop on the oil-soaked beaches of Louisiana.

So what prompted the advisory committee to vote against approval by a resounding 10-6 majority? It’s a bit of a story in itself, one that started earlier in the same room, where the fate of the diabetes drug rosiglitazone (Avandia) was discussed and vigorously debated for two days. Vivus’ Qnexa was the closing act to follow a bitterly contested decision of whether to keep GlaxoSmithKline’s Avandia on the market—a matter that was in balance due to the question of whether the drug increases risk of cardiovascular events—events that were foreseen by some and contested by others, but which took tens of thousands of patients to assess. It is painful for everyone to go back to ask if approving a drug was the right decision. Hindsight is a mean master, and the master had just taught the field a serious lesson.

What lesson? I think if one were to characterize the problem with a phrase, it would be that timeless warning made to physicians in training—”Primum non nocere,” or “First, do no harm”. Another way to say it is—be careful, and make sure you don’t make a decision you’re going to regret. Don’t end up in the same tense room 10 years later trying to figure out what, if anything, went wrong.

Yes, there were signals and other concerns with Vivus’ treatment, falling into a few main categories inherent to the two molecules packaged … Next Page »

Tom Hughes is CEO of Cambridge, MA-based Zafgen. Follow @

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  • http://www.mangiasano.org Leoluca Criscione

    Dear Tom,
    We should rather educate people!!!
    This is the lesson i learned from the 10 years obesity research experience.
    We wrote a book about the topic with the title “Eating healthy and dying obese”, (available in german, italian and soon in english).
    A chapter reads “science feeds the confusion”. Another chapter is about my own studies eating McDonald’s and loosing weight and eating healthy foods (5000 kcal like supersize me author) and gaining 3.2 kg in a week!
    I wellcome the decision of the FDA to reject ANY drug to reduce weight!