Arena Pharma And The Fat Lady's Song

My primary concern is the drug's modest effect size. In Arena's Phase III studies, named BLOOM and BLOSSOM, lorcaserin recipients lost only 3.7% and 3.0% of their body weight, respectively, after adjusting for the placebo group (all patients in the study also had intensive dietary counseling). That's not a very big impact, especially given the baseline demographics (patients, roughly 80% of whom were female, weighed 220 lbs on average).

For comparison, patients treated with Vivus'(VVUS) Qnexa -- a combination of phentermine and the anti-seizure medication topiramate that also received a positive Advisory Committee vote this year -- lost 3.5% to 9.3% of baseline body weight in the company's two Phase III trials, depending on the dose (Vivus explored three doses). Qnexa should receive FDA approval this year as well and will also likely need a REMS; the drug's PDUFA date is in mid-July.

Bulls will point out that 23% of lorcaserin-treated patients in BLOOM lost more than 10% of baseline body weight at one year, compared to only 8% of patients in the control arm (the results from BLOSSOM are similar). Those data are, in my view, the primary reason for lorcaserin's positive FDA panel vote (I consider safety an enabling factor; toxicity can prevent approval, but a drug must show some evidence of efficacy to get a favorable recommendation). Unfortunately, many patients regained significant weight in the second year of the BLOOM trial (one third of the "responders" that lost ≥ 5% of baseline body weight failed to maintain that threshold after two years). Lorcaserin induces major, sustained weight loss in only a tiny subgroup of patients.

Of further concern is the fact that, even in the tightly controlled environment of Arena's pivotal trials, 43% of patients in the lorcaserin arms dropped out after one year; an additional 25% of "completers" included in the second year of the BLOOM trial dropped out early as well. Nearly all of the discontinuations were explicit or implicit patient choice unrelated to side effects. (Far fewer patients in Vivus' Phase III trials stopped treatment early.) This worrying statistic suggests that obese patients either don't perceive lorcaserin's effect or showcases obesity's rampant recidivism. I suspect both, but either way, it's not good for lorcaserin's commercial prospects; discontinuation rates will skyrocket once the drug is on the market (patients in clinical trials receive extremely intensive care to minimize dropouts).