Following a planned review by an independent Echocardiographic Data Safety Monitoring Board (EDSMB), Arena Pharmaceuticals, Inc. said it would continue BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management), a pivotal trial evaluating the efficacy and safety of lorcaserin hydrochloride for the treatment of obesity.
The EDSMB's review of unblinded echocardiographic data performed after patients completed 12 months of dosing in the trial confirmed that differences, if any, in the rates of Food and Drug Administration (FDA)-defined valvulopathy in patients treated with lorcaserin and in the control group did not meet the EDSMB's predetermined stopping criteria. Based on the EDSMB's review of the rate of FDA-defined valvulopathy, Arena has been able to confirm that the statistical power calculations used in the design of the phase III trial programme to monitor patients for increased risk of developing valvulopathy are justified. The findings from the month-12 review build on the EDSMB's September 2007 review that evaluated echocardiograms after 6 months of dosing.
"This critical milestone assessing month-12 echocardiographic adata strongly supports lorcaserin's cardiovascular safety profile. We believe that this exposure duration, even under a conservative interpretation of the literature, would have been sufficient to observe a fenfluramine like effect on heart valves if present. BLOOM's primary echo endpoint is based on the month-12 data," said Jack Lief, president and chief executive officer, Arena. "We are committed to continued efforts to develop a robust database for submission to the FDA in our efforts to provide patients a novel, safe and effective obesity treatment."
BLOOM, the first of three lorcaserin phase III trials, is a double-blind, randomized, placebo-controlled trial involving nearly 3,200 patients in approximately 100 centers throughout the United States. The trial is evaluating a 20 mg daily dose (10 mg dosed twice daily) of lorcaserin versus placebo over a two-year treatment period in obese patients (Body Mass Index, or 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 proportion of patients with a 5 per cent or greater weight reduction from baseline at week 52 is the primary efficacy endpoint. Patients received echocardiograms at screening, 6 months and 12 months after initiating dosing in the trial, and will receive follow-up echocardiograms at 18 and 24 months. There are no further planned EDSMB meetings.
The BLOSSOM (Behavioral modification and Lorcaserin Second Study for Obesity Management) trial is evaluating 10 mg and 20 mg daily doses (10 mg dosed once or twice daily) of lorcaserin versus placebo over a one-year treatment period in obese patients with or without co-morbid conditions and overweight patients with at least one co-morbid condition at about 100 sites in the United States.
The BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial is evaluating 10 mg and 20 mg daily doses (10 mg dosed once or twice daily) of lorcaserin versus placebo over a one-year treatment period in obese and overweight patients with type 2 diabetes at about 45 sites in the United States.
As in the BLOOM trial, diet and exercise are also included in the BLOSSOM and BLOOM-DM trials, and the primary efficacy endpoint is the proportion of patients with a 5 per cent or greater weight reduction from baseline at week 52. Arena is also studying several key secondary endpoints, including changes in serum lipids and HbA1c and, in the BLOOM-DM trial, other indicators of glycemic control.
In both of these additional trials, all patients will receive echocardiograms at baseline, at month 6, and at the end of the study to assess heart valve function over time. In contrast to the BLOOM trial, however, there are no echocardiographic exclusion criteria and there is no monitoring by an independent monitoring board. The lorcaserin phase III pivotal programme is planned to enrol a total of approximately 7,000 patients.
"The month-12 review of the echocardiographic data significantly adds to our confidence in lorcaserin's cardiovascular safety profile," said William R. Shanahan, M.D., vice president and chief medical officer, Arena. "BLOOM is scheduled to complete about one year from now, and I'm looking forward to additional data demonstrating the potential of this novel compound to address weight loss in a highly targeted manner."
Lorcaserin, Arena's internally discovered oral drug candidate for the treatment of obesity, is in an ongoing phase III programme. The compound is the first in a new class of obesity drug candidates targeting the 5-HT2C serotonin receptor, which is located in the hypothalamus, a key area of the brain associated with regulation of food intake and metabolism. Results from phase II studies demonstrated that treatment with lorcaserin produced highly statistically significant, progressive and dose-dependent weight loss over a 12-week period. Lorcaserin was generally well tolerated at all doses in the phase II clinical trials and had no apparent effects on heart valves or pulmonary artery pressure.