There were mixed reactions from investors and analysts after Arena Pharmaceuticals released top-line results from a Phase III clinical trial with its obesity treatment lorcaserin.

The results from the BLOSSOM (Behavioural modification and LOrcaserin Second Study for Obesity Management) trial showed that patients taking lorcaserin 10mg twice daily lost 5.9% on average of their body weight, compared with the average 2.8% lost by patients on placebo.

Looked at another way, 47.2% of patients treated with lorcaserin 10mg twice daily lost at least 5% of their body weight compared with 25.0% of the placebo group. Arena said this met the efficacy benchmark in the most recent draft guidance from the US Food and Drug Administration (FDA) on developing products for weight management. The company plans to file a New Drug Application for lorcaserin with the FDA in December.

Some commentators were equivocal, though, a stance reflected by the fall in Arena’s share price on the back of the results announcement, then subsequent recovery following an upbeat conference call.

Arena’s confidence that it was in line with FDA guidance on weight-management products was not universally shared. Specifically, the draft guidance from February 2007 says a product can generally be considered effective for weight management if, after one year of treatment, either:

- the difference in mean weight loss between the active and placebo groups is at least 5% and that difference is statistically significant; or
- the proportion of trial subjects who lose greater than or equal to 5% of their baseline body weight in the active-product group is at least 35%, is approximately double the proportion in the placebo group, and the difference between groups is statistically significant.

Clearly the BLOSSOM trial fell short on the first set of criteria. Whether 47.2% of patients in the lorcaserin arm qualified as “approximately double” the 25.0% with weight loss of at least 5% in the placebo group is a matter of conjecture.

The Associated Press quoted Lazard Capital Markets analyst Terence Flynn as saying that the results “appear to be on the border of the criteria recommended by the FDA”.

Flynn also noted that the difference in weight loss between patients on lorcaserin and placebo was smaller than the margins seen in studies with Orexigen Therapeutics’ Contrave (naltrexone + bupropion) and Vivus’ Qnexa (phentermine plus topiramate) – rival drugs in late-stage development for the lucrative weight management market.

In patients on lorcaserin 10mg twice-daily who completed the 52-week BLOSSOM trial according to protocol, 63.2% lost at least 5% of their body weight, compared with 34.9% of patients on placebo, Arena reported. Those in the active group lost an average of 17.0 pounds, or 7.9% of their total body weight.

The efficacy outcomes echoed the previously reported results of the BLOOM (Behavioural modification and Lorcaserin for Overweight and Obesity Management) trial, as did the drug’s safety profile. In particular, rates of FDA-defined valvulopathy, or heart valve damage, in the BLOSSOM trial at week 52 were 2.0% for patients on lorcaserin 10mg twice daily, 1.4% for those on lorcaserin 10mg once daily, and 2.0% for the placebo group.

There had been concerns about the safety of Arena’s drug as its mode of action is similar to that of fenfluramine, one of the two active ingredients in Fen-phen, the anorectic combination withdrawn from the market in 1997 after being linked to heart valve damage.

The BLOSSOM trial included 4,008 patients with an average body mass index of 35.9 and baseline weight of 220 pounds. The BLOSSOM and BLOOM studies together evaluated 7,190 patients for up to two years.