Arena’s Lorcaserin Has Safety Edge

Results from Arena’s (ARNA - Analyst Report) phase III BLOSSOM study are strikingly similar to the BLOOM study, with mean total weight loss for the 10mg lorcaserin BID group coming in at 17.0 lbs in BLOSSOM vs. 17.9 lbs in BLOOM. These equated to 7.9% and 8.2% mean absolute weight loss. The placebo was 3.9% and 3.4% in each trial, respectively, putting the mean placebo-adjusted weight loss for each trial at 4.0% and 4.8%. Total categorical weight loss for the completer analysis was 63.2% in BLOSSOM and 66.4% in BLOOM, vs. 34.9% and 32.1% for the placebo.

Per the FDA draft guidance: “A product can be considered effective for weight management if after one year of treatment either of the following occurs: (1) the difference in mean weight loss between the active-product and placebo-treated groups is at least 5% and the difference is statistically significant, or (2) the proportion of subjects who lose greater than or equal to 5% of baseline body weight in the active-product group is at least 35%, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant.

Data from the BLOSSOM and BLOOM confirms that lorcaserin successfully meets the second criteria for approvability. However, perhaps even more important than efficacy, the safety and tolerability profile of lorcaserin in the completed phase III program was outstanding.

The biggest concern going into the phase III development with lorcaserin was the potential for increased rates of valvulopathy (what took down Phen-Fen). Completed 52-week data demonstrates no apparent affect on heart value function for lorcaserin patients.

Plus, a significant benefit of lorcaserin over both Vivus’ (VVUS - Analyst Report) Qnexa and Orexigen’s (OREX - Snapshot Report) Contrave is that lorcaserin requires no four-week titration. This is because of the uniquely benign side-effect profile of the drug.

Adverse events (AEs) were surprisingly low for the combined program, with no specific event exceeding the placebo by > 4%. Both Qnexa and Contrave have a significant number of AEs that exceed 5% placebo adjusted, including dry mouth, tingling, constipation and altered taste for Qnexa and nausea, headache, constipation, vomiting and insomnia for Contrave. Serious adverse events in the lorcaserin phase III program were infrequent and did not differ statistically from placebo. Neuropsychiatric events, depression, mood alteration and suicidal ideation were all also similar to placebo.

Although the efficacy of lorcaserin is shy of Qnexa and Contrave, we believe the unique safety and tolerability profile make the drug a very attractive partnering asset for a large-cap pharmaceutical company. We expect that Arena will see to file the U.S. NDA (new drug application) alone by the end of the year and then partner prior to approval in 2010.

Expect Combination Use with Phentermine

According to data from Arena, Phentermine held approximately 80% of the prescription market share for obesity scripts in 2008. Other molecules including orlistat, sibutramine, topiramate and bupropion round-out the top-5.

Vivus’ Qnexa, a combination of phentermine and topiramate, clearly looks like the most efficacious drug. However, we believe that head-to-head, lorcaserin offers greater efficacy and far better tolerability than topiramate.  Therefore, we believe the number one treatment option for obesity scripts post approval of lorcaserin will be a combination lorcaserin-phentermine product.

Our biggest concern is that Arena does not intend to conduct a safety analysis of lorcaserin and phentermine together, choosing to keep lorcaserin as a single agent and defer any additional studies to its commercial partner.

Whether or not the U.S. FDA will request additional safety data on lorcaserin or on a potential “Phen-Lor” product remains to be seen. This could be a stumbling block for Arena next year when the FDA reviews the drug. More information and a detailed head-to-head presentation of all three post-phase III obesity drugs can be found in our full research report.