Belviq/lorcaserin NASH data to be presented at AASLD Liver Meeting

The following poster will be presented at the Liver meeting this weekend w/ over 10,000 participants:



Lorcaserin Improves the NASH Clinical Score in the Majority of High-Risk Patients: A Retrospective Analysis of Three Phase III Studies

Poster Number: 462

This post-hoc analysis evaluated the ability of lorcaserin to improve NASH (nonalcoholic steatohepatitis) clinical score and liver function test parameters (ALT, AST) in overweight or obese patients with and without type 2 diabetes mellitus.





Lorcaserin Improves the NASH Clinical Score in the Majority of High-Risk Patients: a Retrospective Analysis of Three Phase 3 Studies

Wajahat Z. Mehal1, Randi Fain2, Alan Glicklich3, Yuhan Li2, William Shanahan3, William Soliman2; 1Yale University, New Haven, CT; 2Eisai, Inc., Woodcliff Lake, NJ; 3Arena Pharmaceuticals, Inc., San Diego, CA



Background: Moderate weight loss has been shown to result in histologic improvement in non-alcoholic steatohepatitis (NASH). Lorcaserin is a selective 5-HT2C agonist approved for chronic weight management. Three large, double-blind, randomized studies (BLOOM: N Engl J Med. 2010;363:245- 56; BLOSSOM: J Clin Endocrinol Metab. 2011;96:3067-77; BLOOM-DM: Obesity. 2012;20:1426-36) have demonstrated the effectiveness of lorcaserin in inducing weight loss in patients with a body mass index of 27 to 45. We conducted a retrospective analysis to determine the ability of 52 weeks of lorcaserin 10 mg bid to improve NASH. The NASH clinical score predicts the presence of histologic NASH and was used as an indicator of NASH activity. Methods: Data were pooled from 3 clinical trials of similar design comparing lorcaserin and placebo in overweight or obese patients with or without type 2 diabetes (NCT00603902, NCT00395135, NCT00603291).



All patients received diet and exercise counseling. The modified intent-to-treat/last observation carried forward population was analyzed for patients with both baseline and end of treatment

NASH clinical score data. Liver parameters (ALT, AST) and weight loss in the MITT/LOCF population were assessed as % change from baseline. The NASH clinical score was analyzed

by comparing proportions of patients shifting from high or very high scores at baseline (NASH-pos) to low or intermediate scores (NASH-neg) at week 52. Results: Approximately 7% of control (182/2519) and lorcaserin-treated (190/2702) patients had a high-risk NASH clinical score, and both groups had an AST/ALT ratio of 0.9. Lorcaserin-treated patients showed significant improvements vs placebo in ALT (% change from baseline to week 52, -2.4 vs 3.0), AST (0.1 vs 2.6) as well as significant weight loss (-5.8 vs -2.4), all P<0.001. In an analysis of the time course of treatment effect, significant weight loss with lorcaserin vs placebo was seen as early as week 2, with peak effect at week 36; peak effect of lorcaserin on liver enzyme levels was at week 24. Significantly more patients treated with lorcaserin (120/190, 63.2%) vs placebo

(89/182, 48.9%) switched from NASH-pos at baseline to NASH-neg at week 52 (P=0.006). Conclusions: Lorcaserin treatment for 52 weeks was associated with greater improvement in serum LFT parameters than placebo, and improvement in NASH clinical score in the majority of high-risk patients. Lorcaserin may be a treatment option for overweight/obese patients with non-alcoholic fatty liver disease/NASH.



Disclosures:

Wajahat Z. Mehal - Management Position: Gloabl BioReserach Partners

Randi Fain - Employment: Eisai Inc

Alan Glicklich - Employment: Arena Pharmaceuticals; Stock Shareholder: Arena

Pharmaceuticals

Yuhan Li - Employment: Eisai, Inc

William Shanahan - Employment: Arena Pharmaceuticals; Management Position:

Arena Pharmaceuticals; Stock Shareholder: Arena Pharmaceuticals

William Soliman - Employment: Eisai Inc

Belviq/lorcaserin NASH data to be presented at AASLD Liver Meeting