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...

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Contrave Rejection and Obesity Drugs’ Future

Today’s a somber day for anyone looking to develop a weight-loss medication. Orexigen’s potential obesity drug Contrave has failed to win FDA approval, just as Arena’s Lorqess and Vivus’s Qnexa before it. In other words, none of the big contenders in the diet drug race we’ve been covering for nearly a year has panned out. Contrave came into FDA decision-day with a a glimmer of hope behind it. Last December, an FDA panel voted in favor of approving Contrave, though they recommended that Orexigen conduct a clinical trial after approval to track the drug’s cardiovascular risk. In contrast, Lorqess and Qnexa hadn’t gotten a thumbs-up from the panel. But the agency turned out to be more conservative than its advisory panel. In a so-called Complete Response Letter, FDA told Orexigen it needed to conduct that cardiovascular clinical trial BEFORE Contrave could be approved, not after approval. Orexigen’s stock fell over 70% on the news this morning. “Such a study would be huge, expensive, and would take years, and the request probably means that Contrave will never hit the market,” writes Forbes’s Matthew Herper. So where do we go from here? I hesitate to say that the obesity drug field is dead. We’ll certainly continue to see scholarly papers about promising new obesity drug targets. But on the clinical side, the focus is going to have to shift away from weight loss to treating the conditions that tend to go hand-in-hand with obesity, like diabetes. That’s what could help tip the safety-efficacy balance in a way that leads to new drug candidates being approved by FDA. This is not a new idea- for instance, C&EN contributing editor Aaron Rowe has covered companies’ efforts to mimic bariatric surgery‘s beneficial effects on diabetes with a pill. Pfizer is in Rowe’s story with a potential diabetes drug in clinical trials. The molecule targets an enzyme that reassembles triglycerides. One of its entries at clinicaltrials.gov says it all: “It is anticipated that PF 04620110 will have anti diabetic effects through inhibition of intestinal triglyceride absorption and potentially weight loss.” Pfizer exited obesity drug research in 2008. But it didn’t abandon efforts to treat some of the conditions that make obesity unhealthy. If targeting a certain enzyme happens to help with both diabetes symptoms and weight loss, so much the better. But weight loss isn’t the top...

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Takeda Keeps On Truckin’ With Obesity Drug Research
Dec28

Takeda Keeps On Truckin’ With Obesity Drug Research

This year’s additions to the pile of setbacks in the obesity drug arena are enough to make anybody wonder whether big pharma companies will continue to invest in the field (was it already two years ago that Pfizer exited obesity research entirely?!). But news today of a pact between Takeda and Sanford-Burnham Medical Research Institute suggests the Japanese drug maker is in it for the long haul. Takeda’s agreement with Florida Hospital and Sanford-Burnham Medical Research Institute creates a partnership to evaluate potential new obesity drug targets. Today’s deal is the latest in a string of obesity-related investments for Takeda. Haystack readers may recall that Takeda is Orexigen’s partner for the development of Contrave, the weight-loss drug that is awaiting a decision from FDA in the wake of a thumbs-up from the agency’s advisory panel. The company also has a stake in peptides from Amylin Pharmaceuticals as potential obesity treatments, and it is conducting clinical development in Japan for Alizyme’s lipase blocker cetilistat, a next-generation pill to Xenical (orlistat), the drug sold over-the-counter as alli. Takeda’s interest in obesity makes sense given its strong history with type 2 diabetes drugs, a class with close ties to the obesity area. A quick look at Takeda’s pipeline is a whirlwind tour of diabetes drug targets, like glucokinase activators and dipeptidyl peptidase-4 inhibitors. The company has also discovered a protein, TGR5, that could be a target for drugs that mimic gastric bypass surgery‘s ability to control diabetes. And they are behind Actos, the well-known diabetes medication which shares its mechanism of action with Avandia. Unlike Avandia, Actos remains on the market, although FDA is currently investigating its safety. Will Takeda’s strategy pay off? Time will tell- beginning with FDA’s official decision on Contrave by the end of...

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Haystack 2010 Year-In-Review

This Friday, we’re looking back at 2010’s big news in pharma and biotech, both the good and the bad. Check out our picks and be sure to weigh in on what you think we missed. 1. Provenge Approved In April, Dendreon’s Provenge became the first approved cancer immunotherapy. Dendreon CEO Mitch Gold called it “the dawn of an entirely new era in medicine.” And while prostate cancer patients are excited for a new treatment option, the approval is perhaps most exciting for its potential to reignite interest in cancer immunotherapy research. There’s a lot of room for improving the approach—Provenge is, after all, expensive and highly individualized. Now that immunotherapy have been proven to work, there’s hope that the lessons learned in both its discovery and clinical development will aid scientists in inventing even better cancer vaccines. 2. Obesity Field Slims The obesity drug race played out in dramatic fashion in 2010, with three biotech companies-Vivus, Arena, and Orexigen, each making their case for its weight-loss medication before FDA. As of this writing, Orexigen’s drug Contrave seems to be on the surest footing to approval, but longtime obesity-drug watchers know that caution seems to rule the day at FDA, so nothing is a sure bet. Orexigen’s Contrave and Vivus’s Qnexa are both combinations of already-approved drugs, whereas Arena’s Lorqess is a completely new molecule. When C&EN covered the obesity race in 2009, it seemed that Lorqess (then going by the non-brand-name lorcaserin) had the cleanest safety profile, but Qnexa was best at helping patients lose weight. But FDA’s panels didn’t always play out the way folks expected. There were safety surprises- notably the worries about tumors that cropped up in rats on high doses of Lorqess, and the extensive questioning about birth defect risks from one of the ingredients in Vivus’ Qnexa. The fact that FDA’s panel voted favorably for Orexigen’s Contrave, a drug that’s thought to have some cardiovascular risks, generated discussion because FDA pulled Abbott’s Meridia, a diet drug with cardiovascular risks, from the market in October. The dust still hasn’t fully settled. Arena and Vivus received Complete Response Letters from FDA for Lorqess and Qnexa. Vivus has submitted additional documentation and a followup FDA meeting on Qnexa is happening in January. Also to come in January is the agency’s formal decision on Contrave. And if you’re interested in learning about the next wave of obesity drugs coming up in clinical trials, read this story in Nature News. 3. Sanofi & Genzyme: The Neverending Story Speaking of drama, Sanofi’s pursuit of Genzyme has been in the headlines for months now, and promises to stretch well into 2011. The...

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Good News for Contrave, Qnexa Could Be Next

Apparently, third time’s a charm in the obesity drug world. Yesterday afternoon, an FDA advisory panel recommended approving Contrave, an obesity pill being developed by Orexigen Therapeutics and Takeda. The positive vote came just months after two other obesity drugs, Vivus’ Qnexa and Arena Pharmaceutical’s Lorqess, were rejected. There are plenty of caveats to the good news. First, FDA doesn’t always follow the advice of its advisory committees, although most analysts seem confident Contrave will make it onto the market. But Orexigen and Takeda will likely need to conduct a large, post-approval study to track cardiovascular issues, the details of which would be hammered out with FDA. Second, excitement over the next pill for obesity should be tempered with the reality that Contrave has shown only minimal weight loss. Contrave is a combination of two already-approved drugs, the antidepressant buproprion and the addiction treatment naltrexone. All that said, Orexigen stands to collect more money from Takeda if Contrave makes it to the finish line. Takeda paid just $50 million upfront to license the obesity drug, and will take on the lion’s share of the costs of a post-approval study. The thumbs up for Contrave could also be good news for Vivus’ Qnexa, also a combination of two existing drugs (phentermine and topiramate). In July, an FDA advisory committee, concerned about the lack of long-term safety data for the drug, voted against its approval. FDA backed up that decision in October, issuing a complete response letter (its version of a rejection) citing birth defect worries and cardiovascular risks. But yesterday’s panel was mainly focused on the cardiovascular risks associated with Contrave, and Qnexa is a cleaner drug on that front. One panel member, University of California, Davis, neurologist Michael Ragowski, even said he’d rather prescribe Qnexa versus Contrave. Vivus plans to submit a formal response to the CRL later this month, and FDA would provide its feedback in January. If all goes well, Vivus could gain approval for Qnexa in the second half of 2011, analysts say. Investors seemed optimistic on its chances, as Vivus’ stock is up over 20% in pre-market trading. Orexigen is holding a conference call at 4:15pm this afternoon, to discuss the panel. If anything interesting comes out of it, we’ll be sure to update...

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