FDA Panel Gives Nod to New Diet Drug Lorqess

May 11, 2012— -- SILVER SPRING, Md. -- An FDA advisory committee has voted 18-4, with one abstention, in favor of approving Lorqess as the first new weight-loss drug in more than a decade.

The FDA's Endocrinologic and Metabolic Drugs Advisory Committee on Thursday afternoon voted that the benefits of Lorqess outweigh its risks, despite the modest weight loss provided by the drug and a lack of data to rule out heart valve issues. If approved, lorcaserin would be an option for those with a BMI of 30 or more, or a BMI of 27 with comorbidities related to obesity.

The panelists agreed that lorcaserin caused a statistically significant greater number of patients (more than double) to lose at least 5 percent of their total weight compared with placebo, which is one of the FDA's requirements for approving weight-loss drugs.

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But the difference in weight loss between the lorcaserin group and the placebo group was small -- just a 3.3 percent difference. The placebo group in the company's clinical trials also had diet and exercise counseling, so the difference in between the two groups may have been smaller than what it would be in the real world, some panelists pointed out.

There were some patients dubbed "responders" for whom the weight drug did seem to work particularly well. More than one-third of patients taking lorcaserin lost 11 percent of their weight, or 25 pounds total, according to Lorqess manufacturer Arena Pharmaceuticals.

This is not the first time Lorqess has come before this panel. In 2010, the committee voted against recommending approval for Lorqess, citing a variety of concerns, including a less-than-impressive weight loss and data from animal studies suggesting that Lorqess increased the risk of tumors in rodents. The FDA rejected Arena's application shortly after, asking for more safety data.

Arena submitted new safety data to the FDA, and the advisory committee members, for the most part, were convinced by the new data.

The panel examined data that seemed to link lorcaserin use to mammary adenocarcinoma in rats, but determined the risk for tumors in humans wasn't worrisome.

The panel was not convinced, however, that there were enough data to rule out a link between Lorqess and valvular heart disease. Several panelists suggested that if Lorqess is approved, patients should regularly be screened for heart valve disease via echocardiogram.

Dr. Abraham Thomas, an endocrinologist at Henry Ford Hospital in Detroit and chairman of the panel, said in addition to the valvulopathy concerns, he also worried about how Lorqess might interact with other drugs commonly used by people trying to lose weight.

Cardiovascular risks have long plagued diet drug development. Fen-phen was yanked from the market in the 1990s after reports of heart value issues, and more recently, in 2010 the obesity drug Meridia was pulled from the market after being linked to cardiovascular complications.

An FDA advisory committee recommended in March 2012 that companies that make obesity drugs should rule out excessive cardiovascular risk prior to drug approval. Lorqess was developed prior to that meeting, so its clinical trials weren't designed to capture cardiovascular risk. And panelists seemed to forgive Arena for not having adequate cardiovascular data given that the FDA "moved the goal posts" on obesity trials midway through.

Weight Loss Drug: Weighing Risks, Benefits

Despite the weight loss not being that impressive, many of the doctors on the panel as well as doctors and patients present at the meeting said another weight-loss tool is sorely needed in the fight against obesity.

"We need a broader array of tools, something between cutting calories and cutting the GI tract," Dr. Domenica Rubino, an endocrinologist and director of the Washington Center for Weight Management, told the panel.

One woman, Lisa Sutter, of Washington, told the panel that she was always of normal weight until after she had two children and then found it impossible to get her weight under control. She enrolled in the Lorqess trial in 2007, and soon she found her urges to overeat had all but disappeared.

"My brain switched back to normal again," she said.

She lost 40 pounds in a year. But after she stopped the drug, she gained it all back, and more.

"I don't want to be this fat forever," she told the panel. "Please, I implore you to approve this drug."

When the panel's vote was announced, Sutter quietly wept, grateful that she might have the option to go back on Lorqess.

While the FDA is not required to follow the advice of its clinical trials, it often does.

The company expects to get a decision from the FDA by June 27.

Lorqess is one of three weight-loss drugs vying to be the first new diet drug approved in a decade.

The FDA is expected to make a decision on Qnexa -- a low-dose combination of phentermine and topiramate -- in July. Like Lorqess, Qnexa was at first rejected by the FDA, but Vivus, the manufacturer of Qnexa, submitted new data on the drug's psychiatric and cardiovascular side effects and an FDA advisory committee endorsed approval by a 20-2 vote in February.

The makers of the third weight-loss drug, a naltrexone/bupropion combination pill called Contrave, announced in 2011 that it won't market Contrave in the U.S. because the FDA's additional requests for data are too burdensome.

The FDA is being particularly vigilant before approving new anti-obesity drugs because if approved, they would likely be very widely used given the nation's obesity epidemic.

New data presented this week at the CDC's Weight of the Nation conference estimated that about 42 percent of adults will be obese by 2030.