Arena Pharmaceuticals reports that a Phase III trial with its weight-management drug, lorcaserin, significantly increased excess weight loss, improved markers of cardiovascular risk and glycemic parameters, and was not associated with depression or suicidal ideation. The company’s stock rose just over 4% in early morning trading.
Additional subgroup analyses showed that lorcaserin caused the greatest improvements in lipid profiles, glycemic parameters, and other markers of cardiovascular risk in patients in the highest risk categories.
“Based on the results from lorcaserin's pivotal program, physicians and patients can expect treatment with lorcaserin along with a lifestyle modification program to result in average weight loss of nearly 20 pounds and a significant reduction in their excess weight over one year, while improving important risk factors and quality of life,” according to Steven R. Smith, M.D., co-principal investigator of the Phase III trial. “Lorcaserin was very well tolerated; the most common side effect was mild and transient headache early in treatment.”
This is the first of three lorcaserin Phase III trials. It was a double-blind, randomized, placebo-controlled study in approximately 100 sites in the U.S. The study evaluated 3,182 patients with an average BMI of 36.2 and baseline weight of 220 pounds. 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. About 55% of patients on lorcaserin completed the 52-week trial compared to 45.1% of patients on placebo.
The data showed that lorcaserin increased excess weight loss during the first year of the trial. Those who received lorcaserin and completed the trial according to protocol lost 31% of their excess weight compared to 12% for the placebo group.
In addition to the previously announced improvements in glycemic parameters, including fasting glucose, fasting insulin and HOMA-IR, lorcaserin patients also achieved highly significant improvements in HbA1C over one year of treatment.
Lorcaserin demonstrated no increase in depression or suicidal ideation compared to placebo, according to Arena. “Drug candidates that act on the central nervous system are currently under tremendous scrutiny for any association with depression or suicidal ideation,” comments Christen M. Anderson, M.D., Ph.D., vp of clinical development. “Lorcaserin's selective activation of an important receptor associated with reduced food intake avoids these liabilities.”
Lorcaserin is a single agent that acts as a selective serotonin 2C receptor agonist. The serotonin 2C receptor is expressed in the brain including the hypothalamus, an area involved in the control of appetite and metabolism. Stimulation of this receptor is associated with feeding behavior and satiety.