New Weight Loss Drug Shows Promise

Modest Weight Loss Seen in Some Patients Taking Taranabant

By Salynn Boyles
WebMD Medical News

Reviewed by Louise Chang, MD

Jan. 8, 2008 -- An experimental weight loss medication in the same class as the drug Acomplia helped patients lose weight in a 12-week, phase II study, but side effects were common at higher doses.

Like Acomplia (rimonabant), which is approved for sale in Europe but not in the U.S., the Merck & Co. drug taranabant targets receptors in the brain linked to appetite.

Concerns about reports of anxiety and depression in rimonabant users have kept the drug off the market in the U.S.

Based on these reports, an FDA advisory panel voted against recommending its approval last June, prompting manufacturer Sanofi-Aventis to withdraw its application to the agency.

Depression and anxiety were also reported in the taranabant study, but these side effects were most common at the highest doses given, researcher Steven Heymsfield, MD, of Merck Research Laboratories, tells WebMD.

Based on these findings, an ongoing phase III trial of taranabant does not include the highest doses used in phase II study.

Taranabant Trial

The double-blind study included 533 obese people randomly assigned to treatment with either placebo or 0.5 milligrams, 2 milligrams, 4 milligrams, or 6 milligrams of taranabant. All the participants received counseling on diet and exercise throughout the trial.

At the end of 12 weeks, the placebo-treated participants had lost the least weight and those treated with the highest dose of taranabant had lost the most.

Patients treated with 0.5 milligrams of the drug lost an average of 3.5 pounds, compared with 5 pounds among people treated with 2 milligrams of the drug and almost 9 pounds among those treated with 6 milligrams.

A total of 27% of patients who took 0.5 milligrams of taranabant lost 5% or more of their body weight, compared with 61% in the 6-milligram group.

But patients taking the higher dosages of the drug also had higher rates of side effects, including anxiety, nausea, and vomiting.

The study drop-out rate due to side effects was also twice as high among patients treated with the highest dosage of the drug, compared with the lowest dose (10.2% vs. 4.7%). But no patients dropped out because of serious events.

The study appears in the January issue of the journal Cell Metabolism.

Heymsfield says he was surprised to find that patients treated with the lowest dose of the drug lost weight.

"We didn't expect weight loss at all doses," he says.

Seeking FDA Approval

The ongoing phase III trial includes roughly 2,000 people being treated with taranabant at doses ranging from 0.5 milligrams to 2 milligrams, a Merck spokeswoman tells WebMD.

She adds that the plan is to petition the FDA for approval in the second half of this year if the phase III results prove promising.

A spokeswoman for Sanofi-Aventis says several phase III trials of rimonabant are also under way, and the findings could help address the FDA advisory panel's safety concerns about the drug.

Julissa Viana tells WebMD that the company will likely petition the FDA once again to approve the drug for sale in the United States.

"I can't speculate on when we will submit or what those indications [for use] will be," she says. "We are looking forward to the results of our ongoing trials."

Weight loss specialist Louis Aronne, MD, says the FDA may be more likely to approve the drug the second time around as safety issues are addressed.

Aronne directs the comprehensive weight control program at New York-Presbyterian/Weill Cornell Medical Center.

"Rimonabant is now approved in 51 countries, and it is being actively sold in 20," he says. "I think as time goes on and the evidence builds that this class of drugs has a manageable side effect profile, the FDA will become more comfortable with it."

Reference Link:

http://www.webmd.com/diet/news/20080108/new-weight-loss-drug-shows-promise