By COLLEEN CREAMER
For VerusMed
Merck & Co. Inc. is discontinuing its clinical development program for the investigational obesity drug taranabant based on data from Phase III trials that showed the drug’s efficacy did not outweigh its side effects.
As reported previously, in a 12-week Phase III trial that included 533 obese patients who were treated with placebo or taranabant at a dose of 0.5 mg, 2 mg, 4 mg or 6 mg, taranabant led to statistically significant weight loss as compared with placebo, but there was also a trend across dose in gastrointestinal adverse events and psychiatric-related events. The authors of the study noted that the onset of both types of events tended to be early and that the trend of adverse events due to depressed mood/depressive symptoms, depression, insomnia and irritability for all evaluated doses was not statistically significant.
In a separate Phase III study of 2,502 obese patients with the obesity-related comorbidities hypertension, dyslipidemia or sleep apnea, the patients were treated with placebo or taranabant at the same doses for as long as 104 weeks.
In that trial, an independent Data and Safety Monitoring Committee found that the 6 mg dose did not provide significantly greater efficacy relative to the 4 mg dose and showed a trend toward a higher side-effect profile. The patients in the 6 mg dose group were subsequently re-randomized to receive the 2 mg dose or placebo. By week 36, the patients treated with the 2 mg dose had achieved their maximum weight loss and maintained the loss for another 16 weeks.
However, gastrointestinal adverse events, the most frequently reported side effects, were more common among the taranabant-treated subjects than in the placebo group, and psychiatric events and irritability also occurred more often among the patients who received taranabant. The patients who took 4 mg and 6 mg of taranabant reported significantly more affect, anxiety and depression than did the patients who took placebo.
“Available Phase III data showed that both efficacy and adverse events were dose related, with greater efficacy and more adverse events in the higher doses,” said Dr. John Amatruda, head of diabetes and obesity research at Merck Research Laboratories. “Therefore, after careful consideration, we determined that the overall profile of taranabant does not support further development for obesity.”
Sanofi-Aventis Group withdrew its New Drug Application for rimonabant, which is marketed as Acomplia outside of the United States, in June 2007 after a Food and Drug Administration committee chose not to recommend approval of the drug because of its potential to increase the chances of suicidal ideation and seizures. Taranabant and rimonabant are of the same drug class.
–From VerusMed.com
