Lorcaserin (Belviq) has become the first obesity drug approved for use in the United States since orlistat in 1999. The excitement that surrounds any new obesity therapy is understandable; the obese and overweight patient population is huge, growing in number and without effective drugs.
Lorcaserin is designed to target specific serotonin receptors that induce weight loss without resulting in valvulopathy the side-effect that led to the market withdrawal of dexfenfluramine and fenfluramine in 1997. The review process has rumbled on for a long time; back in September 2010 the FDA's Advisory Committee voted 9-5 against the approval of lorcaserin. After trialing lorcaserin in more than 7,000 patients in the clinical development program Arena provided enough evidence to satisfy the FDA that the risk of serious adverse events was acceptably small. At lorcaserin's second FDA Advisory Committee meeting on May 10, 2012, the panel voted 18-4 in favor of approval which was granted on June 27, 2012.
In light of currently available data the side-effect profile of lorcaserin is relatively clean. No major causes for concern have become apparent during the Phase III clinical trial program. The modest weight loss offered by lorcaserin has meant the FDA has had to very carefully scrutinize the risk-benefit profile of the drug. On average, patients in the lorcaserin treatment group lost 3% more of their body weight than the placebo group. After a year of lorcaserin treatment 47% of non-diabetic patients lost 5% of their body weight but so did 22.6% of the placebo group. Further questions arise from trials that extended lorcaserin use to a second year where rather than further weight loss, the mean weight of patients rebounded slightly towards the baseline value.
From a clinical perspective it would be fair to say that lorcaserin's weight loss is not great but is certainly better than nothing. Importantly, lorcaserin is associated with small improvements in a number of cardiovascular risk markers which will by viewed favorably by physicians. When it comes to making a market assessment for lorcaserin problems arise when we factor into the equation out-of-pocket costs and patients weight loss expectations. Obesity drugs are poorly reimbursed meaning the majority of patients that take lorcaserin will have to pay for it themselves. Discontinuation of weight loss therapy leads to weight regain so once a patient takes an obesity therapy they may be required to take it indefinitely. Paying several hundred dollars a year to lose 6-8lbs is not a tempting offer for the typical obese patient and historically, poor adherence and discontinuation rates in obesity are evidence of this.
As with most drugs there are strong responders and patients that respond well to lorcaserin who will be more inclined to continue treatment. After a year of treatment in Phase III trials 22% of non-diabetic obese patients lost >10% of their body weight. The obese patient population is big enough to support multiple drugs but lorcaserin will experience competition from the more efficacious Qnexa and cheap phentermine generics.
Events are moving quickly in obesity: Arena and Eisai have committed to enter lorcaserin into a post-marketing cardiovascular outcomes trial (CVOT), Orexigen has already begun enrollment for Contrave's (bupropion/naltrexone) CVOT as part of a pre-approval requirement. If Qnexa is granted approval in July we will soon be entering an extremely exciting period where three obesity drugs will be under study in large CVOTs. To date no obesity therapy has survived a CVOT without serious safety issues coming to light. Hopefully the new batch of emerging therapies will manage to demonstrate the long term benefits of pharmacologically induced weight loss and help treat a substantial unmet medical need.