FDA: Endocrinologic and Metabolic Drugs Advisory Committee

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.