Phase 3 Results: BLOOM
In our BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) trial, lorcaserin patients achieved highly significant categorical and absolute weight loss in Year 1, and continued treatment with lorcaserin in Year 2 helped over two-thirds of patients maintain their 5% or greater weight loss. Treatment with lorcaserin also resulted in highly significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk. Lorcaserin was very well tolerated, did not result in increased risk of depression and was not associated with the development of cardiac valvular insufficiency.
Efficacy
Lorcaserin demonstrated strong efficacy in patients who completed one year of treatment according to the trial’s protocol:
- 66.4% of lorcaserin patients lost at least 5% of their body weight, compared to 32.1% for placebo, and the average weight loss in this responder population was 26 pounds.
- 36.2% of lorcaserin patients lost at least 10% of their body weight, compared to 13.6% for placebo.
- Average weight loss of 8.2% of body weight, or 17.9 pounds, was achieved in the lorcaserin group, compared to 3.4%, or 7.3 pounds, for placebo.
Using an intent-to-treat last observation carried forward (ITT-LOCF) analysis, patients treated with lorcaserin achieved highly statistically significant categorical and average weight loss after 12 months:
- 47.5% of lorcaserin patients lost at least 5% of their body weight, compared to 20.3% for placebo. This result satisfies the efficacy benchmark in the most recent FDA draft guidance, which provides that a weight-management product can be considered effective if after one year of treatment the proportion of patients who lose at least 5% of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.
- 22.6% of lorcaserin patients lost at least 10% of their body weight, compared to 7.7% for placebo.
- Average weight loss of 5.8% of body weight, or 12.7 pounds, was achieved in the lorcaserin group, compared to 2.2%, or 4.7 pounds, for placebo.
Safety and Tolerability Profile
Treatment with lorcaserin was very well tolerated, resulting in very few adverse events with greater frequency than the placebo group. The most frequent adverse events reported in Year 1 and their rates for lorcaserin and placebo patients, respectively, were as follows: headache (18.0% vs. 11.0%), upper respiratory tract infection (14.8% vs. 11.9%), nasopharyngitis (13.4% vs. 12.0%), sinusitis (7.2% vs. 8.2%) and nausea (7.5% vs. 5.4%). Adverse events of depression, anxiety and suicidal ideation were infrequent and were reported at a similar rate in each treatment group.
Cardiovascular Safety
The assessment of echocardiograms indicated that lorcaserin was not associated with valvular insufficiency: during two years of use, rates of change in individual regurgitant scores and the development of FDA-defined valvulopathy were similar between treatment groups. Rates of new FDA-defined valvulopathy in BLOOM were as follows: lorcaserin 10 mg twice daily (2.7%) and placebo (2.3%) at Week 52 and lorcaserin 10 mg twice daily (2.6%) and placebo (2.7%) at Week 104.
Secondary Endpoints
Treatment with lorcaserin over one year was associated with highly significant improvements compared to placebo in multiple secondary endpoints, including:
- Blood Pressure: systolic blood pressure, diastolic blood pressure and heart rate
- Lipids: total cholesterol, LDL cholesterol and triglycerides
- Glycemic Parameters: fasting glucose, fasting insulin and insulin resistance
- Inflammatory Markers of Cardiovascular Risk: high-sensitivity CRP and fibrinogen
Patient Disposition
BLOOM evaluated 3,182 patients with an average Body Mass Index (BMI) of 36.2 and baseline weight of 220 pounds. The Week 52 completion rate was higher for patients on lorcaserin (54.9%) compared to patients on placebo (45.1%). Discontinuation rates for adverse events were similar in the lorcaserin and placebo groups for Year 1 and Year 2 (7.1% vs. 6.7% and 3.0% vs. 3.0%, respectively).
BLOOM Trial Design
BLOOM, the first of three lorcaserin Phase 3 trials, was a double-blind, randomized, placebo-controlled trial involving 3,182 patients in approximately 100 sites in the US. The trial evaluated 10 mg of lorcaserin dosed twice daily versus placebo over a two-year treatment period in obese patients, BMI 30 to 45, with or without co-morbid conditions and overweight patients, BMI 27 to less than 30, with at least one co-morbid condition. The trial did not include any dose titration or run-in period. Patients were randomized in a 1:1 ratio to lorcaserin or placebo at baseline. At Week 52, 856 patients taking lorcaserin were re-randomized in a 2:1 ratio to continue lorcaserin or to switch to placebo, and 697 patients on placebo were continued on placebo. Patients received echocardiograms at screening, and at 6, 12, 18 and 24 months after initiating dosing in the trial. Patients with FDA-defined valvulopathy were excluded from enrolling in the trial.
(This page was last updated: January 5th, 2010. Additional information regarding Arena is available in its SEC filings.)
