FDA Mulls More Obesity Drugs

The US Food and Drug Administration set dates for advisory committees to review three new anti-obesity drugs by year end. FDA will announce its decision on two of them in the next few months.

Alexis Pellek

First up: Qnexa

Vivus (Mountain View, CA) is developing Qnexa (phentermine/topiramate) to control appetite and satiety. The drug is a combination of the appetite suppressant phentermine (of the infamous fen-phen diet pill) and topiramate, the active ingredient in Johnson & Johnson's (New Brunswick, NJ) antiseizure medication Topamax. Weight loss is one of Topamax's side effects, and the drug is also used to treat migraines.

On July 15, 2010, the Endocrinologic and Metabolic Drugs Advisory Committee convened to assess the risk–benefit profile of Qnexa. Vivus is seeking approval of the drug for the treatment of obesity in adults in conjunction with proper diet and exercise and is recommended for use with related comorbidities of hypertension, diabetes, and dyslipidemia. High-, medium-, and low-dosage formulations were studied in clinical trials. The advisory committee determined, in a vote of 10–6, that the potential side effects of Qnexa overshadow the potential benefits.

It wasn't that Qnexa was ineffective in clinical trials; on the contrary, participants lost an average of 10.6% of their weight while taking the highest dose for one year compared with 1.7% for those taking a placebo. Patients taking the medium dose lost 8.4% and those taking the low-dose formulation lost 5.1% of their weight.

The advisory panel's concerns focused on the safety of the drug, given the likelihood that millions of people might take the medication long term for weight loss. Side effects of concern to the committee included: psychiatric issues such as depression, anxiety, and suicidal thoughts; cognitive adverse effects such as impaired memory; cardiovascular effects such as increased heart rate and palpitations; metabolic acidosis, which is the buildup of acids in the body that could lead to kidney stones; and the potential for birth defects.

In the evaluation of whether to approve Qnexa, FDA has a tough decision on its hands. Side effects of the drug are worrisome, but so are the health risks involved with obesity. Two-thirds of Americans are obese or overweight, according to the Centers for Disease Control and Prevention. Approving Qnexa could represent another tool in the fight against the ever-increasing public-health crisis of obesity, but it could also place a large portion of the population at risk. It seems FDA may have to choose between the lesser of two evils.

The agency will decide whether to approve Qnexa by Oct. 28, 2010, which is the Prescription Drug User Fee Act (PDUFA) date for the drug. FDA usually follows the advice of its review panels, but it is not required to do so.

Second for review: Lorcaserin

Arena Pharmaceuticals (San Diego) is waiting for approval of its appetite-curbing drug lorcaserin hydrochloride. This drug is different from the other two anti-obesity drugs under review in that it is a new compound, not a combination of existing, approved medications. Arena inked a deal in July with Eisai (Tokyo) to market lorcaserin and could receive more than one-third of Eisai's net sales and up to $1.37 billion in other payments if the drug is approved. FDA's advisory panel will meet on Sept. 16, 2010, to discuss lorcaserin, and Oct. 22, 2010, is the PDUFA date (one week before Qnexa).

Third in line: Contrave

The third obesity drug to come under review this year, Contrave (naltrexone sustained release [SR]/bupropion SR), by Orexigen Therapeutics (San Diego), will be evaluated by FDA's advisory committee on Dec. 7, 2010. The drug, like Qnexa, is a combination of two existing drugs. It consists of naltrexone, which is used to fight cravings in alcohol and drug addiction treatment, and the antidepressant medication bupropion. Contrave is designed to focus on the body's metabolism and the ability to control eating habits. Contrave's PDUFA date is Jan. 31, 2011.

Drugs alone are unlikely to solve America's obesity crisis, but the need for options is great. It is possible that three additional approved therapies could help America turn the tide in the fight against fat.

Alexis Pellek is an assistant editor of Pharmaceutical Technology.