FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)
The message from the panelists was that not enough data was available to assuage concerns about safety, as well as concerns about how the drug would work in a wider population.
This marks the second thumbs-down for a prospective obesity drug this year. Vivus’s drug candidate Qnexa received a ‘no’ vote from the panel in July.
Going into the yesterday’s panel, the mood wasn’t exactly sunny. As I wrote yesterday, the FDA briefing documents for lorcaserin contained an unexpected safety surprise. The agency was concerned about malignancies that cropped up in rats taking high doses of lorcaserin. And Arena’s stock had tanked on the news.
At the panel, Arena tried to allay FDA’s concerns right off the bat- in its presentation to the panel, the company said that the tumors were attributable to rat-specific mechanisms, so they wouldn’t apply to people. The company even presented a slide listing FDA approved drugs that showed higher rates of rat cancers than lorcaserin (I do not have this information but will update if I get it). The company reiterated that in clinical trials, patients taking lorcaserin did not have an increased risk of cancer.
FDA’s briefing documents also contained a safety note about heart valve problems. As I’ve written before, lorcaserin had a lot to prove in this department. It targets the same serotonin receptor as fenfluramine, an ingredient in the infamous Fen-Phen obesity drug combo. Fenfluramine was associated with heart valve damage and a fatal lung disorder- it was pulled from the market in 1997.
But lorcaserin is different from fenfluramine- it is more selective for one specific subtype of serotonin receptor and avoids the one that’s found in the heart. Arena had surmised that this would help avoid the valve problems that plagued fenfluramine, and the company has had to pay special attention to heart valve safety throughout lorcaserin’s development. The reason FDA is concerned is that their statistical analysis of Arena’s heart valve data (using a different method from Arena) suggests a risk for heart valve damage for patients on lorcaserin. FDA said the company could not statistically rule out a 50% increase in the risk of heart valve problems. At the panel, Arena defended its own data and statistics and said it was committed to continued safety monitoring in a post-approval period.
But at the end of the day, it was the safety-efficacy balance that led to the thumbs-down vote from FDA’s panel. As I wrote back in 2009, lorcaserin met some but not all of FDA’s specific weight-loss benchmarks. It may just be that for a drug that is only mildly effective, the safety bar gets pushed up still higher in panelists’ minds. And with what panelists saw as a lack of sufficient data on safety as well as data on the drug’s effects in broader patient populations, it was too much of a risk to say ‘yes’ to lorcaserin.
In a post-meeting statement, Jack Lief, Arena’s chief executive, defended lorcaserin. “Arena and Eisai believe that lorcaserin has a positive benefit-risk profile,” he stated. “Arena will work closely with the F.D.A. as the agency completes its review.”
After the decision came down, I had a great discussion on Twitter with Matthew Herper of Forbes. Here is what we said, with links added for context:
carmendrahl: If lesson of the $ARNA #Lorqess panel is that for #obesity drugs, more data is key, I’ve gotta wonder who’s got the $ to do that nowadays.
matthewherper: @carmendrahl lorca always had the problem that it had to prove it lacked a side effect. never a good place to start.
carmendrahl: @matthewherper True that. Interesting that topiramate in Qnexa has a side effect spectre (birth defects) as well.
matthewherper: @carmendrahl It’s just a really tough field. The drugs do have to be so safe. And tolerable. I mean, who uses Xenical?
carmendrahl: @matthewherper Agreed. But I think scientists will always be thinking about new drug targets with hope that history doesn’t repeat itself.
As for what’s next, FDA will make decisions about Arena’s Lorqess and Vivus’s Qnexa in October. The agency has more choices than just approving or rejecting the drugs outright. It could request more data in what’s called a complete response letter. But this will drag out the regulatory process and cost companies precious cash.
On that topic, in a note to investors commenting on Arena, Leerink Swann analysts Steve Yoo and Joshua Schimmer wrote that given the panel’s decision, no sales of lorcaserin are likely to take place before 2013. They expect Arena to start cost-cutting measures and to attempt to raise more capital.
That’s it for now. Once again I’d like to thank Adam Feuerstein of TheStreet and Lisa LaMotta of Minyanville for liveblogging the panel proceedings. Plenty of tweets/blogs were coming from the panel but I found their work most useful.