The Food and Drug Administration on June 27 approved the obesity drug lorcaserin hydrochloride despite concerns that it might increase the risk of valvulopathy.
Lorcaserin (Belviq), a selective serotonin 2C receptor agonist manufactured by Swiss drug maker Arena Pharmaceuticals, was approved at a dosage of 10 mg twice a day as an adjunct to diet and exercise for weight management in adults with a body mass index of at least 30 kg/m2 or at least 27 kg/m2 with weight-related comorbidities.
More than one-third of American adults are considered obese, defined as having a BMI of at least 30, according to the Centers for Disease Control and Prevention.
According to Arena and Eisai Inc., which will distribute the drug, the FDA has recommended that lorcaserin be classified by the U.S. Drug Enforcement Administration as a scheduled drug.
The companies said in a statement that once the DEA has determined the final scheduling, Eisai will say when the drug will be available to patients and physicians.
The approval is a long time in coming, and after two advisory committee meetings were held about the drug. In September 2010, the majority of the committee voted against approval, expressing concerns about marginal weight loss and about a trial population that did not reflect the likely real-world use of the drug. In May of 2012, the committee met again. Although a majority was in favor of approval, there were lengthy discussions about the higher rate of valvulopathy associated with lorcaserin treatment in trials. Many called for further study of that issue, and the panel also recommended that patients be monitored with echocardiography at baseline and periodically during treatment.
Citing those concerns, Public Citizen’s Health Research Group sent a letter to the FDA on the eve of approval, urging the agency to reject the drug.
The FDA said it took safety issues into account, and noted in a press release announcing the approval that when the drug is used at the approved dose, it "does not appear to activate the serotonin 2B receptor." Activation of that receptor on heart tissue appears to have been the reason for valvulopathy that occurred in patients who took the weight loss drugs fenfluramine and dexfenfluramine, which were removed from the market in 1997.
The agency also said that valve function was assessed by echocardiography in 8,000 patients in lorcaserin trials and that there "was no statistically significant difference in the development of FDA-defined valve abnormalities between Belviq and placebo-treated patients." However, the drug will be labeled to be used with caution in patients with heart failure.
Arena is also being required to conduct six postmarketing studies, including a long-term cardiovascular outcomes trial.
In studies, when compared with those taking a placebo, patients taking lorcaserin for up to a year had an average weight loss of 3%-3.7%, said the FDA. Almost half of nondiabetic patients lost at least 5% of their body weight, compared with less than a quarter of those taking a placebo. Of the subjects with type 2 diabetes, 38% taking lorcaserin lost at least 5% of their body weight, compared with 16% taking a placebo.
The labeling recommends that lorcaserin be discontinued in patients who fail to lose 5% of their body weight after 12 weeks. They are "unlikely to achieve clinically meaningful weight loss with continued treatment," according to the FDA.
The drug also should not be used during pregnancy. Side effects may include serotonin syndrome, particularly when lorcaserin is taken with therapies that increase serotonin levels or activate serotonin receptors, such as antimigraine drugs or antidepressants.
According to Arena and Eisai, lorcaserin may also cause problems with thinking, sleepiness, confusion, and, in higher doses, hallucinations, euphoria, or disassociation. It may also cause priapism, so it should be used with caution in men who are predisposed to the condition, said the companies.