The FINANCIAL -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) reported on September 18 positive, highly significant top-line results from the BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management) trial. BLOSSOM confirms the results previously reported for the BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) trial and completes the lorcaserin Phase 3 pivotal registration program of 7,190 patients evaluated for up to two years.

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Arena plans to submit a New Drug Application, or NDA, for lorcaserin to the US Food and Drug Administration, or FDA, in December.

 

In the one-year BLOSSOM trial, lorcaserin met all primary efficacy and safety endpoints. Patients achieved highly significant categorical and absolute weight loss. Lorcaserin was very well tolerated and was not associated with depression or suicidal ideation. The integrated echocardiographic data set from BLOSSOM and BLOOM rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA. Treatment with lorcaserin also resulted in significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk.

 

"Today there are extremely limited options to meet the needs of physicians and patients in the real world clinical practice of weight management," said Steven R. Smith, M.D., Executive Director of the Florida Hospital Clinical Research Institute. "Physicians need options that have the potential to help the typical obese patient lose significant weight by staying on a safe and well-tolerated treatment. The clinical data show lorcaserin is a solution that could provide physicians with a weight-loss medication applicable for broad use in the majority of their patients who need to lose weight and improve their health. BLOSSOM demonstrated that nearly two-thirds of lorcaserin patients lost a medically meaningful amount of body weight while avoiding unwanted side effects and a complicated titration program."

 

"History has taught us that the marriage of efficacy and safety is of critical importance in treating patients. Neither is sufficient without the other. With its excellent safety and tolerability profile, we expect lorcaserin to change the way primary care doctors treat the broad cross-section of overweight and obese patients with pharmacotherapy," said Jack Lief, Arena's President and Chief Executive Officer. "With the completion of our robust Phase 3 pivotal program, we will focus on the NDA filing, work with the FDA during the review process and prepare for the commercialization of lorcaserin."

 

Arena plans to present detailed data from both the BLOOM and BLOSSOM trials at the 27th Annual Scientific Meeting of The Obesity Society, scheduled for October 24-28 in Washington, D.C.

 

Efficacy

 

Per Protocol Results

 

Lorcaserin was highly effective in helping patients achieve significant weight loss using multiple measurements. Patients treated with 10 mg of lorcaserin dosed twice daily (BID) who completed the 52-week trial according to protocol demonstrated the benefit of long-term treatment with lorcaserin:

 

    --  63.2% of patients lost at least 5% of their body weight (p<0.0001);

    --  35.1% of patients lost at least 10% of their body weight (p<0.0001);

    --  Patients lost an average of 17.0 pounds, or 7.9% of their body weight;
        and

 

    --  The quartile of lorcaserin patients with the greatest weight loss (among
        those with a Week 52 weight recorded) lost an average of 35.1 pounds, or
        16.3% of their body weight.

 

Of the placebo patients who completed the trial, 34.9% and 16.1% achieved at least 5% and 10% weight loss, respectively, and the average weight loss was 8.7 pounds, or 3.9%. The top quartile of lorcaserin patients lost 36% more body weight than the top quartile of placebo patients.

 

For the patients treated with 10 mg of lorcaserin dosed once daily (QD) and completing the 52-week trial according to protocol, 53.1% lost at least 5% of their body weight and 26.3% lost at least 10% of their body weight. The average weight loss in the lorcaserin 10 mg once daily group was 14.3 pounds, or 6.5%. As with the higher dose, all results were highly statistically significant (p<0.0001 compared to placebo).

 

Intent-to-Treat Last Observation Carried Forward (ITT-LOCF) Results

 

Measurements of efficacy using ITT-LOCF analysis also showed that lorcaserin met all primary endpoints. This analysis includes all patients who were randomized and returned for at least one weight measurement. Patients treated with 10 mg of lorcaserin once or twice daily achieved highly statistically significant categorical and average weight loss after 12 months:

 

Lorcaserin 10 mg Twice Daily

 

    --  47.2% of patients treated with 10 mg of lorcaserin dosed twice daily
        lost at least 5% of their body weight compared to 25.0% for placebo
        (p<0.0001). 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 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 patients treated with 10 mg of lorcaserin dosed twice daily
        lost at least 10% of their body weight compared to 9.7% for placebo
        (p<0.0001);

 

Lorcaserin 10 mg Once Daily

 

    --  40.2% of patients treated with 10 mg of lorcaserin dosed once daily lost
        at least 5% of their body weight (p<0.0001); and

 

    --  17.4% of patients treated with 10 mg of lorcaserin dosed once daily lost
        at least 10% of their body weight (p<0.0001).

 

Patients who took lorcaserin 10 mg twice daily achieved an average weight loss of 5.9% of their body weight, compared to 2.8% for placebo (p<0.0001). Similarly, patients who took lorcaserin 10 mg once daily achieved an average weight loss of 4.8% of their body weight (p<0.0001).

 

BLOSSOM Confirms BLOOM

 

In BLOSSOM, as in BLOOM, lorcaserin's excellent tolerability allowed patients to begin treatment at the full dose immediately, without a titration period, and achieve rapid weight loss. As in BLOOM, significant weight loss compared to placebo was shown at the first trial visit, two weeks following randomization.

 

"Lorcaserin demonstrated consistent results in the BLOOM and BLOSSOM trials, which together evaluated nearly 7,200 patients for up to two years," said William R. Shanahan, M.D., Arena's Vice President and Chief Medical Officer. "These results support lorcaserin's potential to meet the need for a safe, effective and well-tolerated weight loss medication. There are only two drugs that are approved by the FDA for long-term treatment, and new mechanistic and better tolerated approaches could greatly improve the treatment of patients who are obese or significantly overweight."

 

Safety and Tolerability Profile

 

Lorcaserin was very well tolerated. No adverse event rate in the lorcaserin group exceeded the placebo group by more than 4%. The most frequent adverse events and their rates for patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were as follows: upper respiratory infection (12.7%, 14.5%, 12.6%); nasopharyngitis (12.5%, 11.7%, 11.8%) and headache (10.0%, 10.5%, 7.6%).

 

Adverse events of depression, anxiety and suicidal ideation were infrequent and were reported at a similar rate in each treatment group. Serious adverse events, or SAEs, occurred infrequently: one death occurred in the placebo group, no SAEs of seizure were reported and the number of neuropsychiatric SAEs in lorcaserin patients did not exceed the number in the placebo group.

 

Cardiovascular Safety

 

The integrated BLOOM and BLOSSOM echocardiography data set rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA. Echocardiographic evaluations showed no association between lorcaserin and the development of heart valve insufficiency. Rates of new FDA-defined valvulopathy in BLOSSOM at Week 52 were as follows: lorcaserin 10 mg twice daily (2.0%), 10 mg once daily (1.4%) and placebo (2.0%).

 

"The echocardiographic safety data show no risk of valvulopathy," commented Neil J. Weissman, M.D., Director, Cardiac Ultrasound and Ultrasound Core Labs, President, MedStar Research Institute, and Professor of Medicine, Georgetown University. "In the individual and combined BLOOM and BLOSSOM data sets there is no evidence of a difference in the development of valve disease in lorcaserin patients versus control for up to two years of continuous use. No prospective echocardiographic program has ever studied this many patients for this period of time."

 

Secondary Endpoints

 

Treatment with lorcaserin over one year was associated with significant improvements or strongly favorable trends compared to placebo in multiple secondary endpoints, including blood pressure and lipids.

 

Patient Disposition

 

BLOSSOM evaluated 4,008 patients with an average body mass index, or BMI, of 35.9 and baseline weight of 220 pounds. The Week 52 completion rate was higher for patients on lorcaserin 10 mg twice daily (57.2%) and 10 mg once daily (59.0%) compared to patients on placebo (52.0%). Discontinuations for adverse events were low and as follows: lorcaserin 10 mg twice daily (7.2%), 10 mg once daily (6.2%) and placebo (4.6%).

 

 

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