FDA raises safety issues for Lorcaserin approval

Modest Weight Loss, Safety Issues May Put Lorcaserin Approval in Peril
Modest weight loss and safety questions, including that of a possible link to valvular heart disease, will be at the forefront of today’s advisory committee discussion on whether to recommend approval of Arena’s lorcaserin.
Although the weight loss observed in the lorcaserin-treated patients generally improved their blood pressure, glucose and insulin levels, as well as levels of high sensitivity C-reactive protein, FDA reviewers expressed concerns about the drug’s safety and overall effect on weight loss, according to briefing documents.
Lorcaserin is a new molecular entity that targets activation of the serotonin 5HT2C receptor and is intended to promote weight loss in an obese population. Agonism at the intended target, 5HT2C, is reasonably demonstrated to underlie the anorexigenic effect of lorcaserin. An important aspect of the preclinical development program for lorcaserin was the assessment of receptor selectivity for 5HT2C relative to other serotonin receptor subtypes, particularly other members of the 5HT2 receptor family 5HT2A and 2B. Relative to drug action, the 5HT2A and 2B receptors are implicated in contributing to the hallucinogenic and addictive responses to drugs of abuse (5HT2A), and to drug-induced valvulopathy including that associated with use of dexfenfluramine in humans (5HT2B).

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM225631.pdf