New England Medical Journal peer review on Lorcaserin

Boldface is my emphasis.

ABSTRACT

Background: Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight.

Methods: In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed.

Results: At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8±0.2 kg with lorcaserin and 2.2±0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar.

Conclusions In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo.

Editorial:

The justification for using lorcaserin to manage obesity is not greater efficacy than currently available drugs, but rather an apparently much better safety and adverse-event profile and very clear-cut beneficial effects on risk factors for type 2 diabetes and cardiovascular disease. Where lorcaserin will fit into the management of obesity remains to be seen. Future studies could investigate the potential for improved weight-loss efficacy by combining lorcaserin with other receptor-selective weight-loss compounds such as analogues of glucagon-like peptide 1. Given the history, we will need to be doubly sure about the safety of lorcaserin, used either alone or in combination with other weight-loss drugs.

Valvulopathy is why fen-phen was withdrawn in 1997, after 18 million subscriptions were written in 1996. Pfizer (formerly Wyeth, formerly American Home Products) set aside $21 billion for class action lawsuits.

The potential for a weight management treatment is staggering. Perform your own due diligence.

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Disclosure: no position in PFE. Long shares of ARNA. Short put options in ARNA.