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From Blog: The Haystack

Avandia’s Reckoning Day

After years of debate over the safety of GlaxoSmithKline’s diabetes drug Avandia, U.S. and European regulatory agencies have finally made a decision about the future of the drug. European authorities have recommended suspending marketing of the drug, while FDA is severely restricting access to the drug, but seems to be leaving the door open to further actions. GSK, meanwhile, issued a press release saying it would stop promoting Avandia worldwide.

Today’s announcements mark yet another chapter in the Avandia saga, which began in May 2007, when Cleveland Clinic cardiologist Steve Nissen published an analysis of the combined data from 42 previous clinical trials of GSK’s diabetes drug. The results weren’t pretty: Nissen’s article in the New England Journal of Medicine claimed that patients taking Avandia were 43% more likely to have a heart attack than those who were not on the pill. The next three years brought a series of safety alerts, conflicting data analyses, advisory panels, and questions over whether GSK tried to cover up the cardiovascular safety risk associated with the drug.

In July, a panel of FDA advisors had mixed views on Avandia: 12 of the 33 panelists voted to remove the drug from the market, while 10 said it could stay on the market with strong restrictions on prescribing the drug.

FDA today sided with those 10 panelists and imposed strict limitations on who can take Avandia. The agency will also adjust the drug’s label to reflect the safety risk. Under a risk evaluation and mitigation strategy, or REMS, Avandia can only be prescribed to new patients if they have been unable to control their blood sugar with other diabetes drugs. Continue reading →

From Blog: The Haystack

Future Cloudy for GSK’s Avandia

A panel of FDA advisors decided yesterday that GlaxoSmithKline’s diabetes drug Avandia should either be withdrawn from the market or its use seriously restricted. The panel had been assembled after several years of ongoing questions over the safety of the drug, which has been linked to an increased risk of cardiovascular events.

The final vote came down to this: 12 panel members said the drug should be removed from the market, while 10 said it could stay on the market, but with strong restrictions on who could both prescribe and take the drug. The remaining members voted to either keep the label the same or revise it somehow to better reflect the safety concerns.

With that mixed bag in hand, its up to FDA to decide what to do.

For those of you having trouble keeping track of the ins an outs of the Avandia story, here’s a little primer. GlaxoSmithKline’s Avandia problems—the public ones, at least—began in May 2007, when the safety of the drug was questioned by Cleveland Clinic cardiologist Steve Nissen, previously known for blowing the lid off the cardiovascular issues associated with Merck’s arthritis drug Vioxx. In an article in The New England Journal of Medicine, Nissen said an analysis of the combined data from 42 previous clinical trials of Avandia showed that patients taking the drug were 43% more likely to have a heart attack than those who weren’t. FDA issued a safety alert about the drug, which brought in $3 billion for GSK in 2006.

In August 2007, an FDA advisory panel voted 22-1 to keep Avandia on the market. Still, Avandia franchise sales fell 22% to $2.4 billion in 2007.

But GSK’s troubles with Avandia go beyond the financial pain of lost sales. As you might expect, the company is at the receiving end of a flood of lawsuits related to the drug. It could get worse. This week, the NY Times said it had reviewed internal documents suggesting GSK knew as early as 1999 that the drug posed a safety risk, but actively worked to conceal those findings from FDA. Yesterday, GSK said it would take a charge of $2.36 billion in the second quarter, in part to help pay to settle lawsuits related to Avandia and its antidepressant Paxil.

Avandia works by lowering blood glucose levels by increasing cells’ responsiveness to insulin. This isn’t the first time drugs acting on Avandia’s target, the peroxisome proliferator-activated receptor (PPAR), have run into safety trouble. In 2005, Merck and Bristol-Myers Squibb withdrew a New Drug Application for their PPAR agonist Pargluva after FDA asked for a five-year cardiovascular safety study. And Warner-Lambert pulled the drug Rezulin from the market in 2000 after it was shown to cause liver toxicity.

From Blog: The Haystack

Takeda’s Diabetes Drug Candidate TAK-875 In Phase III Trials

Takeda Pharmaceutical today announced it has begun Phase III clinical trials of TAK-875, a first-in-class drug candidate for treating type 2 diabetes. The experimental therapy activates GPR40, a G-protein-coupled receptor that resides in pacreatic islet cells.

The TAK-875 story is as much about the biology of the target as it is about the molecule itself. And it’s a story that owes much to the company’s willingness to delve into uncharted territory.

In the early 2000s, scientists knew GPR40 existed, but didn’t know what GPR40′s purpose was in the body. Plenty of proteins fit this description– they’re called “orphan receptors” in the industry parlance. Much of Takeda’s drug discovery strategy is based on figuring out what orphan receptors do.

In a 2003 paper in Nature (DOI: 10.1038/nature01478), Takeda laid out what it learned about GPR40. The receptor responds to a variety of long-chain fatty acids. In response to fatty acid binding, GPR40 activates and boosts insulin secretion from pancreatic beta cells.

GPR40 became a viable drug target for Takeda for several reasons. First, one of the hallmarks of type 2 diabetes is a reduction in insulin secretion from pancreatic beta cells, something GPR40 activation could help counter. Second, G-protein-coupled receptors are established drug targets– and GPR40 happens to be in the class of GPCRs for which researchers know the most about structure– the Class A, or rhodopsin-like, GPCRs. (Note: other GPR-type receptors are diabetes targets as well– C&EN contributing editor Aaron Rowe has written about Arena Pharmaceuticals’ activators of GPR119 as diabetes drug candidates.)

TAK-875 docked to a model of GPR40 (ACS Med. Chem. Lett.)

Takeda used structural knowledge to its advantage in the discovery of TAK-875 (ACS Med. Chem. Lett., DOI: 10.1021/ml1000855). Researchers were able to build a model of GPR40 based on its similarity to GPCRs of known structure, and dock potential drug candidates inside to see how well they could bind.

This is far from the only drug discovery story that has to do with “de-orphanizing” orphan receptors. In fact, as far back as 1997, pharmaceutical company researchers were writing about orphan receptors as a neglected drug discovery opportunity (Trends Pharmacol. Sci., DOI: 10.1016/S0165-6147(97)90676-3). And of course, just because researchers have “de-orphanized” a receptor doesn’t mean all of the complex biology is pinned down. Case in point: the PPAR receptors (J. Med. Chem., DOI: 10.1021/jm990554g). Despite these receptors’ promise as targets for obesity and diabetes, drugs designed to target them have tanked in development or had unexpected problems after arrival on the market (read: Avandia).

So as TAK-875 enters Phase III trials, the news might be about the drug candidate’s clinical performance, but you can be sure that Takeda’s researchers are still working hard to unravel as much of GPR40′s basic biology as they can behind the scenes.

From Blog: The Haystack

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 January.

From Blog: The Haystack

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 story goes something like this: Genzyme had a tumultuous year, as it struggled to correct the manufacturing issues that created product shortages and eventually led to a consent decree with FDA. In walked Sanofi, who offered—in a friendly way—to buy the company for $18.5 billion. Genzyme refused to consider what it viewed as a lowball offer. Weeks passed, they remained far apart on price with no signs of anyone budging, until Sanofi finally went hostile. Genzyme suggested it would be open to an option-based deal, which would provide more money later on if its multiple sclerosis drug candidate alemtuzumab reached certain milestones. Sanofi stuck to its $18.5 billion guns and is now trying to extend the time period to convince shareholders to consider its offer.

4. Final Stretch in HCV Race

This year, the industry finally got a peek at late-stage data for what are likely be the first drugs approved for Hepatitis C in more than two decades. Based on Phase III data, analysts think Vertex’s telaprevir will have an edge over Merck’s boceprevir once the drugs hit the market. Meanwhile, the next generation of HCV drugs had a bumpier year, with several setbacks in the clinic. Still, the flood of development in HCV has everyone hoping that eventually people with HCV can take a cocktail of pills, rather than the current harsh combination of interferon and ribavirin.

5. Pharma Covets Rare Diseases

Historically, research in rare diseases has been relegated to the labs of small biotechs and universities. But in 2010, big pharma firms suddenly noticed that if taken in aggregate, a pretty sizable chunk of the public—on the order of 6%–suffer from rare diseases. They also noticed that when there’s a clear genetic culprit, drug discovery is a bit more straightforward. Further, rare disease can sometimes be a gateway to approval in larger indications, making them all the more appealing. With that, Pfizer and GlaxoSmithKline both launched rare diseases units and made a series of acquisitions and licensing deals (Pfizer/FoldRxGSK/AmicusGSK/Isis, etc) to accelerate their move into the space. Meanwhile, Sanofi is trying to jump in with both feet through its proposed acquisition of Genzyme.

6. MS Pill Approved

Novartis gained approval in September for Gilenya, the first treatment for multiple sclerosis that is a pill rather than an injection. In even better news for people with MS, there more pills are rounding the corner towards FDA approval: Sanofi’s teriflunomide, Teva’s laquinimod, and Biogen’s BG-12. All of these drugs come with safety caveats, but the idea of new treatment options after years depending on interferons has gotten everyone in the MS field pretty excited.

7. Antibody-Drug Conjugates Prove Their Mettle

The concept of linking a powerful chemo drug to a targeted antibody, thereby creating something of a heat-seeking missile to blast tumor cells, isn’t new. But antibody-drug conjugate technology has finally matured to a point where it seems to be, well, working. Seattle Genetics presented very positive results from mid-stage studies of SGN-35 in two kinds of lymphoma. And ImmunoGen provided clear data showing its drug T-DM1 could significantly minimize side effects while taking down breast cancer.

8. Pharma Forges Further into Academia

With nearly every pharma firm paring back internal research, the focus on external partnerships has never been greater. Broad deals with universities are becoming more common, and Pfizer has arguably gone the furthest to evolve the model for working with academic partners. In May, Pfizer announced a pact with Washington University under which the academic scientists will look for new uses for Pfizer drug candidates. As part of the deal, they gain unprecedented access to detailed information on Pfizer’s compound library. And last month, Pfizer unveiled the Center of Therapeutic Innovation, a network of academic partnerships intended to bridge the “valley of death,” between early discovery work and clinical trials. The first partner is University of California, San Francisco, which scores $85 million in funding over five years, and the network will eventually be comprised of seven or eight partners, worldwide. Most notable is that Pfizer is planting a lab with a few dozen researchers adjacent to the UCSF campus to facilitate the scientific exchange.

9. Finally, New Blood Thinners

This year saw the FDA approval of a viable alternative to coumadin (aka warfarin), a 50-plus-year-old workhorse blood thinner that interacts with many foods and herbal supplements.

Boehringer’s Pradaxa (dabigatran) got a unanimous thumbs-up from an FDA panel for preventing stroke in patients with a common abnormal heart rhythm called atrial fibrillation. FDA approved the drug in October. The next new warfarin alternative to be approved could be Xarelto (rivaroxaban), which has had favorable results in recent Phase III clinical trials, as David Kroll over at Terra Sig explained. Both Xarelto and Pradaxa had already been approved for short term use outside the US.

Rivaroxaban and dabigatran work at different stages of the biochemical cascade that leads to clotting, as we illustrated here. Another drug candidate in the warfarin-alternative pipeline is BMS’s and Pfizer’s apixaban. Check out coverage of apixaban trials here and at Terra Sig. And in a separate blood-thinner class, FDA today rejected Brilinta, a possible competitor to mega-blockbuster Plavix.

10. Alzheimer’s Progress & Setbacks

Alzheimer’s disease has been a tough nut to crack, and news in 2010 has done little to dispel this reputation. This year Medivation’s Dimebon, which started life as a Russian antihistamine and showed some promise against Alzheimer’s, tanked in its first late-stage clinical trial. Later in the year, Eli Lilly halted development of semagacestat after the compound actually worsened cognition in Alzheimer’s patients. Semagacestat targeted the enzyme gamma-secretase, and the New York Times and other outlets reported the news as shaking confidence into a major hypothesis about what causes Alzheimer’s and how to treat it– the amyloid hypothesis.

But not everyone agreed with that assertion. Take Nobel Laureate Paul Greengard, who told C&EN this year (subscription link) that semagacestat’s troubles may have been due to the drug’s incomplete selectivity for gamma-secretase.

This year Greengard’s team discovered a potential way to sidestep the selectivity issue, by targeting a protein that switches on gamma-secretase and steers it away from activities that can lead to side effects. Greengard thinks the amyloid hypothesis is very much alive. But the final word on the amyloid hypothesis will come from trial results in next year and beyond, for drugs such as BMS-708163, Bristol Myers Squibb’s gamma-secretase inhibitor.

11. Avandia (Barely) Hangs On

Avandia was once the top selling diabetes medication in the world, but in 2010 long-running rumblings about the drug’s cardiovascular risks reached fever pitch. By the fall, Avandia was withdrawn from the European Union market and heavily restricted in the US.

Avandia (rosiglitazone) helps diabetics control their blood sugar levels by making cells more responsive to insulin. Widespread scrutiny of Avandia dates back to 2007, when a study led by Vioxx-whistleblower and Cleveland Clinic cardiologist Steve Nissen suggested Avandia increased the risk of heart attacks. In February 2010, a leaked government report that recommended Avandia be pulled from the market made headlines. In July, an FDA advisory panel voted on what to do about Avandia, and the results were a mixed bag, with most panel members voting either to pull the drug entirely or add severe restrictions. In the end, FDA sided with the “restrict” panelists- Avandia is still on the market, but it can only be prescribed to patients who can’t control their blood sugar with a first-line medication.

Clearly, researchers still have a lot to learn about how the drugs in Avandia’s class work. But we enjoyed reading Derek Lowe’s self-characterized rant about just how much effort has been put in so far. Among several other drugs in Avandia’s class, Rezulin (troglitazone) was pulled from the market many years ago because of adverse effects on the liver, but Actos (pioglitazone) remains on the market and appears to be safe.

12. Executive Musical Chairs

The year after a trio of mega-mergers and at a time when patent losses are piling up, drug companies shook up their management. The most notable changes came at Pfizer: First, the company abandoned its two-headed approach to R&D leadership and picked Michael Dolsten, former head of R&D at Wyeth, to lead research. Martin Mackay, Pfizer’s head of R&D, meanwhile jumped ship to lead R&D at AstraZeneca. Then, in a move that took everyone by surprise, Pfizer’s CEO Jeff Kindler suddenly stepped down and Ian Reade took over. At, Merck, president Kenneth Frazier will take over as CEO in January;  Richard T. Clark will stay on as chairman of Merck’s board. And just this week, Sanofi-Aventis saidformer NIH director Elias Zerhouni would replace Marc Cluzel as head of R&D, while Merck KGaA appointed Stefan Oschmann as head of pharmaceuticals. Oschmann comes on from Merck & Co., where he was president of emerging markets.

In the biotech world, the most notable shift came in June, when George Scangos moved over from leading Exelixis totake the top job at Biogen Idec.

13. RNAi Rollercoaster

The year has been a tumultuous one for RNAi technology. Leaders in siRNA technology are experiencing growing pains as they try to turn promising science into commercialized products. Alnylam, arguably the best-known and biggest player in the RNAi arena, laid off 25% of its staff after Novartis decided not to extend its pact with Alnylam. Things only got worse when Roche announced it was exiting RNAi research, a move that hit its development partners Alnylam and Tekmira. Roche seemed to be primarily worried about delivery, an issue that is holding the field back from putting more RNAi-based therapeutics into the clinic.

But it’s not all bad news: the year brought a spate of big-ticket deals for companies developing other kinds of RNAi technology. GSK signed on to use Isis Pharmaceuticals’ antisense technology, which uses single-stranded rather than double-stranded oligonucleotides. And Sanofi entered into a pact with Regulus, the microRNA joint venture between Isis and Alnylam, worth $740 million. Further, Isis and Genzyme made some progress with mipomersen, the cholesterol drug developed using Isis’ antisense technology.

14. Revival of Interest in Cancer Metabolism

In cancer research, the old was new again in 2010, with a flurry of publications about depriving cancer cells of their energy source by taking advantage of quirks in their metabolism. That idea has been around since the 1920′s- when German biochemist Otto Warburg noticed differences in how cancer cells and normal cells deal with glucose. This year, Celgene handed over $130 million upfront for access to any cancer drugs that come out of Massachusetts biotech Agios Pharmaceuticals’ labs. One target in Agios’s crosshairs is an enzyme involved in glucose metabolism- pyruvate kinase M2. In addition to the Celgene/Agios deal, we noted that AstraZeneca and Cancer Research UK are in a three-year pact related to cancer metabolism, and the technology behind GlaxoSmithKline’s much-talked-about $720 million purchase of Sirtris has to do with depriving cells of energy.

15. More Job Cuts

Not to end this list on a sour note, but it wouldn’t be complete without acknowledging the ongoing narrative of layoffs and retooling at drug companies. This year brought brutal cuts at AstraZeneca, GSK, Bristol-Myers Squibb, and Abbott, along with the widespread and ongoing layoffs at Pfizer and Merck. Several features in C&EN looked at the impact the cuts are having on chemists:

How some laid-off pharma chemists migrate to new careers

How academic programs are adapting

And the views from the ground in New England and California, two hotbeds of pharma/biotech (hint- it ain’t pretty).

For more jobs insight, join the discussions happening with Chemjobber and Leigh aka Electron Pusher, and check out their chemistry jobs blog roundtable, which just wrapped today.

From Blog: The Haystack

RNAi Roundup #4

While everyone was focused on Avandia & Qnexa, a spate of RNAi-related news slipped past us:

Tekmira Pharmaceuticals scored a major contract through the U.S. Department of Defense’s Transformational Medical Technologies program. The biotech will use its lipid nanoparticle technology to deliver siRNA tailored to treat the Ebola virua. Tekmira could snag up to $34.7 million over the next three years to help bring the Ebola virus candidate through an investigational new drug filing and a Phase I clinical trial. If the government decides to extend the contract beyond Phase I, Tekmira is eligible for up to $140 million in funding. The contract comes a few months after Tekmira and the U.S. Army Medical Research Institute of Infectious Diseases published an article in The Lancet showing its lipid nanoparticle could protect non-human primates against the Ebola virus.

Nitto Denko of Japan and Fremont, Calif.-based Quark Pharmaceuticals will jointly develop RNAi-based drugs to treat fibrotic diseases. The companies will use Quark’s RNAi technology and patent fortress, and Nitto Denko’s drug delivery technology. Terms weren’t disclosed, but the companies say they “have an initial budget of double-digit million US dollars” with the goal of filing their first investigational new drug application with FDA by early 2012. Nitto, which has expertise in polymeric formulations, says it picked Quark because of the chemical modification it had made to the siRNA that have eliminated worries over an immune response from the therapeutic.

AstraZeneca has extended its siRNA research pact with Silence Therapeutics by one year. The companies have worked together since 2007 on finding five novel siRNA therapeutic molecules for oncology and respiratory diseases. The duo forged a separate pact around siRNA delivery in April.

–The NIH has awarded RXi Pharmaceuticals a small business innovation research grant (SBIR) worth $600,000 to support the pre-clinical development of RNAi-based therapeutics. NIH has seen a surge in applications for SBIR grants amid a tougher financing climate for biotechs. RXi is eligible for an additional $1 million per year for up to three years during the second phase of the SBIR’s program.

Alnylam Pharmaceuticals has dosed its first patient in a Phase I clinical trial of ALN-TTR01, a systemically-delivered RNAi therapeutic for the treatment of transthyretin (TTR)-mediated amyloidosis, a rare, inherited disease in which a mutation in the TTR gene causes the build up of the toxic protein in the several tissues in the body. This study is designed to test the safety of the drug and show whether the drug is impacting TTR levels in the blood.

From Blog: The Haystack

Safety Data On Vivus’s Qnexa Doesn’t Cut It For FDA Panel-UPDATED

You have to feel for the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee this week. They’d just finished the Avandia slog, but there was no rest for the weary. No, instead, they got to sink their teeth into the first of the potential new obesity drugs, Vivus’ Qnexa.
In a vote that signals safety is king in the obesity drug realm, Qnexa got a thumbs down from the panel this afternoon. The panel was split, with 7 members recommending that FDA should approve the drug and 9 recommending against approval.

The panel’s take home message was that a lack of safety data led to their decision.

Several journalists live-blogged the panel session. Here are the two play-by-plays I followed:
Lisa LaMotta, Minyanville
Adam Feuerstein, TheStreet

This decision comes after what seemed like an optimistic week for Vivus. On Tuesday, when FDA released its briefing documents about Qnexa, media reports on the data suggested that even though the agency’s review focused on safety, it didn’t look like safety would be a dealbreaker. In a note to investors, Leerink Swann analyst Steve Yoo wrote, “Overall, we believe the language in the FDA briefing documents to be fairly benign, but the FDA is requesting a pregancy category X label that would include contraindication in pregnant women and a warning/ precaution for females of childbearing potential.”

At today’s panel, as expected, nobody really dwelled on Qnexa’s efficacy. But Vivus faced a lot of questions about safety, especially about the effects of Qnexa during a pregnancy. During clinical trials, 13 women on Qnexa gave birth, and none of the babies had birth defects. Because Qnexa is likely to be an appealing option for women of reproductive age if it’s approved, panelists were concerned that more data are needed to make sure Qnexa is safe during pregnancy. That’s because one of the components of Qnexa is topiramate, an epilepsy drug that is known to carry a risk of birth defects. What complicates things is that the dose of topiramate in Qnexa is lower than the dose used for treating epilepsy. It’s also lower than the doses used in studies that suggested topiramate carries a risk of birth defects.

The panel also discussed the other four safety concerns mentioned in the briefing documents:
cardiovascular risks
psychiatric events
cognitive events
metabolic acidosis

But at the end of the day, panelists who voted ‘no’ felt like more long-term safety data was in order. From Feuerstein’s liveblog:

one of the “no” votes says obesity is a chronic disease, so tell me what happens to patients as they stay on the medication for years.

The deadline for FDA to make a decision on Qnexa is October 28. So it might be a while before we hear the final word. Vivus has time to come up with more safety data.

Trading on Vivus’s shares was stopped today because of the hearing but will start again tomorrow. Shares for Arena and Orexigen, the other two big players in the obesity drug race, fell late today. It was a bit of a rollercoaster day for Arena, since shares soared earlier today because of new lorcaserin data published in the New England Journal of Medicine.

UPDATE July 16: Yesterday evening Vivus responded to the news in a conference call. In an accompanying press release, the company noted that “The vote from the Endocrinologic and Metabolic Drugs Advisory Committee is a recommendation. The FDA will take the Committee’s recommendation into consideration during its review of the current application and will make a determination. The FDA may or may not follow the Committee’s recommendation.”

Leland Wilson, Vivus’ CEO, said in the release “We appreciate the Advisory Committee’s recognition of obesity as a significant health crisis, and the challenges associated with the treatment of this disease.”

“We are disappointed with the Advisory Committee’s vote. While the final vote was close, and we are encouraged that the Committee recognized the efficacy demonstrated in the QNEXA clinical trials, we will work closely with the FDA leading up to our October 28, 2010 PDUFA date to address the labeling and safety questions raised during today’s proceedings. We remain committed to patients living with obesity and weight-related disease.”