FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)
Sep17

FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)

Yesterday brought yet another disappointment to the obesity drug development field- an FDA panel recommended rejecting Arena and Eisai's potential diet pill lorcaserin (Lorqess) by a vote of 9 to 5. 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...

Read More
Waiting For Arena, Thoughts On Meridia
Sep16

Waiting For Arena, Thoughts On Meridia

Today the second of three potential drugs in the weight-loss race is in the hot seat- Arena Pharmaceuticals' lorcaserin, which we recently learned will be called Lorqess, if approved. An FDA panel is meeting to decide whether it will recommend the drug for approval. I'm following two liveblogs of the panel, from Lisa LaMotta of Minyanville and Adam Feuerstein of TheStreet.com, and will post my thoughts on the aftermath tomorrow. Obesity drug watchers are looking for clues about today's panel based on one that happened yesterday- that was when Abbott Laboratories' obesity drug Meridia, on the market since 1997, came under FDA's microscope. Meridia works by blocking reuptake of the neurotransmitters serotonin and noradrenalin in the brain, leading to a decrease in appetite. It's effective at helping patients shed pounds, but the drug also boosts blood pressure and heart rate. So doctors and patients have had to deal with a tradeoff between weight loss efficacy and safety (this theme seems to come up a lot in the obesity drug field). Things shifted last November, when a large study called the SCOUT trial suggested that patients on sibutramine had more cardiovascular events compared to patients on placebo. As this WebMD article puts it: The drug is already not supposed to be used in patients with known cardiovascular disease. But experts said they were troubled that many patients with undiagnosed disease could be at greater risk if they use the drug to lose weight. In the aftermath, sibutramine was pulled from the market in the UK and other European nations. And stateside, concern mounted. Which brings us to yesterday's panel. The panel vote was split as to whether to keep sibutramine on the market. Of 16 panelists, 8 voted to withdraw the drug, 2 voted to keep it on the market with more strict warning label language, and 6 voted to keep it on the market with label revisions and restrictions on which doctors can prescribe the drug. (Hat tip to Shelley Wood at theheart.org for getting the vote results up on Twitter asap). So in short, it's not clear to me what will become of Meridia. As for whether the Meridia panel outcome will affect the Lorqess panel today, Leerink Swann analyst Joshua Schimmer wrote in a note to investors that FDA's safety concerns for lorcaserin/Lorqess are likely to be different than the concerns about sibutramine/Meridia. "Because lorcaserin drops both heart rate and blood pressure (albeit in a non-statistically significant manner), we believe the CV issue will not be a major issue," he wrote. But FDA's briefing documents for Lorqess had a safety surprise, which Schimmer says may come into play....

Read More