New evidence about the competition

By: John Scott
Submitted: 2008-05-15 10:33:13
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At the meeting of the American College of Cardiology held in Chicago this March, Merck & Co released some clinical data from the Phase III trials for their proposed competitor to acomplia (rimonabant). This new medication, still going by its generic name of taranabant, targets the same cannabinoid system as acomplia. It is therefore interesting to compare results since, if it gains regulatory approval, it will be a direct competitor to acomplia.

The randomised, double-blind and placebo-controlled trials recruited more than eight hundred participants who all had at least BMI 27. Merck & Co disclosed the preliminary results calculated at the end of year one of what is intended as a two year trial. In conjunction with a diet and exercise program, 28% of those taking a 2mg dose of taranabant lost more than 10% of their body weight, while 57% lost 5% of their body weight. Almost 8% of those on placebo also lost 10% of their body weight through diet and exercise alone. In terms of averages, participants taking a 2mg dose of taranabant lost 14.5 pounds compared to 5.7 pounds on placebo. Depending on how you view these things, this could be viewed as a failure because Merck & Co announced in advance that it was aiming for a minimum 5% body weight loss in all participants taking their medication.

In 2004, Acomplia’s results were that 32% on Acomplia lost more than 10% of their body weight while 62.5% lost more than 5% of their body weight. But these results were obtained at the higher dosage of 20mg as opposed to 2mg taranabant. The reason for the difference in the dosage levels is that acomplia is a CB1 receptor antagonist that blocks endogenous cannabinoid binding to neuronal CB1 receptors, while taranabant acts as a selective cannabinoid-1 receptor inverse agonist, binding to CB1 receptors. I am glad we have got that clear.

Merck & Co also tested higher doses of 4mg and 6mg but admitted problems with psychiatric side effects. It confirmed that taranabant would probably only be brought to the market at the lowest 2mg dose. Because the FDA has already expressed concern about similar side effects in acomplia, the Merck trials looked more specifically for evidence of the effects. It seems that 28% of participants on the 2mg dose reported side effects but it is not known how severe they were.

Because both medications work in a similar way, it always seemed likely that they would have similar problems with central nervous system side effects. Given that acomplia was given a rough ride by the FDA, it would seem unlikely that taranabant will fare any better on the information so far made public. Although both seem to improve the levels of high-density cholesterol and to bring down the level of triglycerides which will help to reduce the risk of heart disease, the fact that both have been associated with feelings of depression and, in some cases, suicide will probably mean that neither will be approved in the US in the near future. Even if the current trials for acomplia produce results with few or no central nervous system side effects, the results of taranabant may still drag acomplia down. If taranabant is also producing unacceptable levels of psychological disturbance at 4mg, acomplia does not look so good at higher dosages.

Nevertheless, this must be placed in a proper context. Acomplia has, of course, been available on prescription in Europe for two years and there is no emerging evidence of problems sufficiently serious to justify withdrawing approval. Indeed, it has just been given a further level of approval in the UK. If acomplia continues to accumulate a positive safety record, this may offset any prejudicial implications in the US from the taranabant trials. What should be relatively uncontroversial is that the use of the cannabinoid system for the treatment of obesity should remain firmly on the research agenda. Acomplia continues to offer an effective supplement to diet and exercise regimes. As its effects are better understood, the reported side effects may be better controlled.

Article source: Expert Articles