Sanofi-Aventis, developer of the highly anticipated weight-loss drug Acomplia (rimonabant), may have stiff competition in only a few years from a similar drug developed by Merck & Co. that is generating some positive buzz in a large late-stage clinical trial.

Unlike Sanofi, which mounted a major public relations campaign around its Phase III trials for Acomplia, Merck has never even announced that it had a cannabinoid CB-1 receptor antagonist in late-stage trials for the treatment of obesity.

But we have learned that Merck has 2,400 participants enrolled in a multicenter, international two-year trial that began in the fall of 2005 of a CB-1 receptor antagonist that it has identified to participants as "L-000899055."

The study is titled: "A 2-Year Study (1-Year Weight Loss Followed by 1-Year Prevention of Weight Regain) to Assess the Safety, Tolerability and Efficacy of L-000899055 in Obese Patients."

A Merck spokesperson, asked about the L-000899055 study and in particular how Merck's CB-1 receptor antagonist might differ from Acomplia, subsequently responded by email that she had "researched our questions" and was not able to provide any information "at this point."

Like Sanofi with Acomplia, Merck appears to be hoping that its CB-1 receptor antagonist helps not just with weight-loss, but with the combination of conditions -- collectively known as metabolic syndrome -- that increase the risk of heart disease.

Under the best of circumstances, Merck's drug -- if it proves as promising as early returns suggest -- seems unlikely to make it through the remainder of testing and the FDA approval process before 2009 at the earliest.

This suggests Sanofi could have a few-year headstart with Acomplia, though it remains unclear what further steps are required for Acomplia to secure FDA approval.

While Merck's has two obesity drugs -- MK-0364 and MK-0557 -- listed on ClinicalTrials.gov's website as in Phase II and III clinical trials, neither is identified anywhere as L-000899055. And L-000899055 is not otherwise identified in the consent forms Merck had patients sign to participate in the trial.

But the length of the L-000899055 trial (two years) -- and the number of participants (2,400) -- would seem to support the belief of several of those taking part that it is a Phase III study. Phase II trials generally involve far fewer participants for a shorter period.

In the consent form that participants were asked to sign, Merck said as of Jan. 2005 once-daily oral doses of up to 6 mg of L-000899055 (the highest dosage being tested in the current trial) or a placebo had been given to over 500 people for 12 weeks. That sounds like a Phase II trial.

Participants in the current Merck trial are men and women, aged 18 and above, with a BMI (body mass index) of between 30 and 43. A BMI of 30 and over is considered obese, 35 and over is considered severely obese, and over 40 is considered morbidly obese.

In the trial, all participants were given a placebo for the first two weeks, after which patients were randomized into one of six groups.

• Those in group one are getting a placebo in the first year and will get a placebo in the second year.
• Those in group two are getting a 4mg dose of the drug once a day in the first year, and will get the same 4 mg dose in the second year.
• Those in groups three through six all are getting a 6 mg dose of the drug in the first year. In the second year:
  • Those in group three will get a placebo.
  • Those in group four will get a 2 mg dose.
  • Those in group five will get a 4 mg dose.
  • Those in group six will get a 6 mg dose.

No minimum exercise program is mandated as part of the trial, nor were participants required to reduce their caloric intake -- though they do get diet counseling once a month.

Anecdotally, participants in the trial say some of those taking part have lost remarkable amounts of weight -- as much as 50 pounds in less than six months.

"This drug has changed my life," one participant told us in an email. "I LOVE this drug!!! Some ask me if I would have to take this the rest of my life. My reply is that I sure hope so."

Participants say they also hear that men are generally losing weight more rapidly than women. The only side effect that seems to have participants talking is that a number of men report feeling more emotional.

In the consent form, Merck said that in its earlier 12-week trial, side effects reported by people taking no higher than a 6 mg dose or a placebo included:

• Nausea
• Loose stools
• Diarrhea
• Vomiting
• Trouble sleeping
• Itchy Skin
• Difficulty concentrating
• Crying
• Depressed mood (feeling sad)
• Anxiety (being worried or nervous)
• Hot flashes or flushing
• Laughing
• Dizziness
• Mood swings (irritability)
• Euphoric mood (feeling full of energy and/or joyful)

One participant told us that while he experienced some nausea in the first week, and a reduced appetite thereafter, the one side-effect he really identified with was the last.

"I have had so much more energy since I began taking this that it is incredible," the participant said.

Outreach: If you are one of those participating in the Merck L-000899055 trial, and would like to share your experiences with us on a totally confidential basis, we would welcome a report on your results to date. If we receive enough reports, we will incorporate them in a follow-up story. Please email your reports to info@AcompliaReport.com.