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FDA panel gives OK to new drug application for obesity
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By an 18-4-1 vote, the FDA’s Endocrinologic and Metabolic Drug Advisory Committee approved a new drug application for lorcaserin hydrochloride, a 5HT2c receptor agonist, indicated for weight management in patients who are obese. However, a post-marketing study will evaluate cited concerns on uncertainty of risk for mammary tumor and valvular heart disease associated with the drug.
According to FDA Briefing Documents, the RR of valvular heart disease in patients assigned lorcaserin was 1.07 (95% CI, 0.74-1.55). Other adverse events associated with use of the drug were a higher incidence for depression as well as suicidal ideation.
Arena Pharmaceuticals, Inc., manufacturer of the tablets provided clinical study designs and patient baseline characteristics, efficacy results and clinical perspective, clinical safety results, preclinical studies and preclinical safety as it relates to human risk.
Edward W. Gregg, PhD, chief of epidemiology and statistics branch at the Division of Diabetes Translation at the CDC, who voted for the approval of the drug, said, “the difference here as opposed to a year and a half ago, when we reviewed this, I think that their work basically did a lot to allay the risks that we were concerned about.”
The drug is indicated for use in patients with BMI ≥30 kg/m2, or BMI ≥27 kg/m2 if accompanied by weight-related co-morbidities.
The first sets of studies were conducted in 2002-2004 in support of early clinical trials, and the second was conducted in 2009 in the course of characterizing metabolites of lorcaserin. A 5% weight loss in 47.5% of patients assigned lorcaserin vs. 20.3% of patients assigned placebo was reported in a phase 3 trial, researchers said.
According to data results, approximately one-third of patients lost approximately 11% or 25 lbs after 52 weeks. Additionally, 50% of lorcaserin patients reached HbA1c≤7% at week 52.
Disclosure: Voting member Dr. Daniel Bessesen of the Endocrinologic and Metabolic Drugs Advisory Committee reports consultancy for a competing firm in a magnitude of $0-5,000 per year. All other voters report no relevant financial disclosures.
Perspective
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George A. Bray, MD
The FDA has two weight loss criteria as well as requirements for safety that they implement in evaluating any drug: 1) The drug must produce a weight loss that is 5% below placebo and this must be statistically significant, 2) And/or the drug must have 35% or more of the patients losing more than 5% body weight, and this must be more than twice the placebo response. Lorcaserin met the second criterion better than the first. Its initial problems were related to tumors in animals, and this still caused some concern for the toxicological experts on the panel.
The tumors were one of the major concerns for this drug, and are still of some concern to the toxicology experts on the panel. From what we know of this drug, it does not appear to have effects of cardiac valves as fenfluramine did, nor does it appear to have neuropsychiatric effects.
Currently there is only one medication, orlistat (Xenical) that is approved by the FDA for long term treatment of obesity. This contrasts with many drugs for treatment of diabetes, dyslipidemia and hypertension. To the extent that physicians can induce and maintain weight loss these other conditions may well be ameliorated and require fewer total medications.
In the drug trials with lorcaserin, the potential for developing valvular heart disease was carefully scrutinized and is certainly one of the outcomes that the FDA is going to continue to follow. There are a large number of trials examining effectiveness of this drug in subpopulations which could be valuable, as well as examining how well it works when combined with orlistat or other medications.
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