LOS ANGELES (Reuters) - Obese patients treated with a low dose of Merck & Co Inc's MRK.N experimental drug taranabant lost a significant amount of weight, but there were side effects, according to interim results from a pivotal trial released by the company on Monday.
After one year, and in combination with diet and exercise, patients given a 2 mg dose of the drug lost an average of 14.5 pounds (6.6 kg), compared with 5.7 pounds for the placebo group.
Patients on the 2 mg pill ended up weighing, on average, 4 percent less than patients on placebo and weight leveled off after 36 weeks.
Higher doses resulted in greater weight loss, but Merck has discontinued study of doses above 2 mg because they increased the incidence of side effects like nausea, irritability and depression without much more benefit in terms of pounds shed.
Taranabant belongs to the same family of medicines as rimonabant, a Sanofi-Aventis SA SASY.PA drug rejected by U.S. regulators last year after it was linked to suicidal thoughts and depression. Both drugs work by blocking cannabinoid receptors in the brain, the same receptors that make people hungry when smoking marijuana.
“We believe we have a different profile ... We didn’t see the same neurological effects in preclinical trials that they did,” said Dr. John Amatruda, vice president of Merck’s metabolism clinical research.
FDA FILING EXPECTED THIS YEAR
He said Merck intends to file this year for U.S. regulatory approval of taranabant, but declined to confirm whether the application would seek a label for weight loss.
Interim results from the 2,500-patient trial showed that 57 percent of patients on the 2 mg dose lost at least 5 percent of their weight, compared with 27 percent of patients given a placebo.
U.S. Food and Drug Administration guidelines call for clinical trials of obesity drugs to show either a mean weight loss of 5 percent versus placebo or that at least 35 percent of patients lose 5 percent or more of their weight, and that the loss be double that of the placebo group.
The trial also found taranabant significantly improved cholesterol levels and reduced the incidence of metabolic syndrome, a cluster of risk factors for heart disease and diabetes.
The obesity trial will continue for another year and Merck expects data from several more pivotal trials -- including doses as low as 0.5 mg and a study in diabetes patients -- over the next several months, Amatruda said.
Sanofi is also conducting additional trials and has said it hopes to submit rimonabant, also known as Acomplia and Zimulti, as a treatment for diabetes worldwide in 2009.
The Merck trial, presented in Chicago at a meeting of the American College of Cardiology, also showed that 2 mg taranabant caused gastrointestinal distress in 42 percent of patients, compared with 29 percent of the placebo group.
Psychiatric disorders and irritability were reported by 28 percent of patients taking 2 mg taranabant, compared with 20 percent of placebo patients.
Amatruda said three patients on the discontinued 6 mg dose reported thoughts of suicide, but the incidence of major depression was actually slightly lower in the 2 mg group than in the placebo group.
Thirteen percent of patients on 2 mg taranabant dropped out of the trial due to side effects, compared with about 8 percent of placebo patients.
Amatruda said Merck remains confident that its clinical development program, which includes a one-year extension for all trials, will be broad enough to address the safety issues brought up by the FDA in its review of rimonabant.
“Our compound appears to be a little more potent ... the weight loss they had with 20 mg is close to what we have with 2 mg,” Amatruda said.
Editing by Braden Reddall
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