Lorcaserin for Obesity

Serotonin plays an important role in the regulation of ingestive behaviour. Lorcaserin (APD356), a potent, selective 5-HT(2C) agonist is currently under development by ARENA pharmaceuticals for the treatment of obesity.

In this month’s issue of OBESITY, Steven Smith and colleagues from the Pennington Biomedical Research Centre, Baton Rouge, LA (where I happen to be visiting today), report on the safety and efficacy of lorcaserin for weight reduction in obese patients.

The randomized, double-blind, placebo-controlled, parallel-arm study enrolled 469 men and women between ages 18 and 65 and with BMI 30-45 . Patients received placebo, lorcaserin 10 mg q.d., lorcaserin 15 mg q.d., or lorcaserin 10 mg b.i.d. for 12 weeks, and were counseled to maintain their usual diet and activity. Safety analyses included echocardiograms at Screening and day 85/study exit.

Lorcaserin was associated with progressive weight loss of 1.8 kg, 2.6 kg, and 3.6 kg at 10 mg q.d., 15 mg q.d., and 10 mg b.i.d., respectively, compared to placebo weight loss of 0.3 kg (P < 0.001 for each group). The proportions of completers achieving >5% of initial body weight were 12.8, 19.5, 31.2, and 2.3% in the 10 mg q.d., 15 mg q.d., 10 mg b.i.d., and placebo groups, respectively.

The most frequent adverse events were transient headache, nausea, and dizziness.

Echocardiograms showed no apparent drug-related effects on heart valves or pulmonary artery pressure.

This short-term study shows that lorcaserin was well tolerated and efficacious for weight reduction.

Obviously, 12 weeks is too short to determine the full efficacy or safety of this compound. Nevertheless, the results appear promising and it will be interesting to see how longer-term studies that combine locaserin with behaviour modification turn out.

AMS
Baton Rouge, LA

Disclaimer: I have served on the locaserin echocardiography data safety monitoring board for ARENA and have received honoraria in this capacity.