Thursday, March 5, 2009

Rimonabant Two Years Later

This week at the American College of Cardiology Scientific Sessions in Orlando, data was presented describing the two-year results with rimonabant in the RIO-Europe trial. Rimonabant, an investigational drug from Sanofi-Aventis, is aimed at helping patients lose weight and quit smoking. Kamagra is a combination of active ingredients which are used to treat erectile dysfunction and premature ejaculation. Thus it helps to maintain erection and prolong the intercourse. Sildenafil and dapoxetine are the main components of this drug. They are characterised by vasodilating and serotonin sustaining effects.Early trials with rimonabant have been promising, but many have cautioned that it\'s way too early to get very excited about this drug. We have to wait for longer-term results, critics said.
Now we have longer term results.
The RIO-Europe trial enrolled and randomized 1507 obese patients to receive either placebo or rimonabant (either 5 mg or 20 mg.) Two years after enrollment, patients taking 20 mg of rimonabant maintained significant reductions in both weight and waist size.
The average weight loss in patients still taking rimonabant was between 15 - 20 pounds (compared to approximately 5 pounds on placebo,) and waist size was reduced by 7.5 cm (compared to 3.4 cm.) Further, patients taking 20 mg of rimonabant after two years had nearly a 30% increase in HDL cholesterol, and a 9% reduction in triglycerides. Perhaps most impressive, the proportion of patients with metabolic syndrome was reduced by 50% in patients on 20 mg of rimonabant. Results on the 5 mg dose also moved things in the right direction, but to a lesser extent.
Side effects were described as minor and temporary, the most frequent being diarrhea, nausea, vomiting and dizziness. More severe anticipated side effects, especially depression, did not materialize.
So, when can we get our hands on this drug?
Critics kept saying: don\'t get excited, we need more data. Well, now we have more data, and if anything the drug is looking even better than previously thought; even the critics seem satisfied now. So when can we get some?
DrRich hates to be a wet blanket, but he has two words for you: Vioxx and Celebrex. Here are two other drugs that were immensely popular, that met a strong unmet clinical need, that looked very good in clinical trials that were at least as large as the rimonabant trials - but, years after they began to be used in very large numbers of patients, turned out to have uncommon, unforeseen, but very serious side effects. And what\'s the result? Patient advocacy groups are screaming bloody murder. Vioxx is off the market and Merck is fighting for survival. Celebrex is still on the market, but barely, and Pfizer is seriously wounded. FDA officials are sweating before congressmen puffed up with righteous anger; heads will roll there. And lawyers are buying second homes in Aspen.
The FDA and Sanofi-Aventis have to be thinking of all this as they decide what to do with rimonabant. The demand for this drug is immense; and contrary to what you might think, especially in the current atmosphere, this huge demand will make both the regulators and the parent pharmaceutical company extremely hesitant about unleashing this drug to the marketplace. Even very rare side effects will show up (and will be made by the media and the legal profession to look common) when tens of thousands begin using the drug - especially when, one can easily predict, patients anxious to lose even more weight will not use the drug quite as prescribed. If the FDA and Sanofi-Aventis have brains in their heads, this drug will initially be approved only for relatively small numbers of patients who are at the highest risk. Most of you reading this, DrRich predicts, won\'t be able to have this drug for quite some time, until its safety profile is much better defined - possibly years from now.
If it\'s any consolation, DrRich points out two things. First, he has no inside information on how this drug will be approved or marketed. He may be dead wrong about this. Maybe it will be a free-for-all after all.
Second, take a look at the data again. The weight loss achieved with rimonabant is highly significant, statistically. But in magnitude, it\'s just not that great. The people enrolled in this study were fat. A 20 pound weight loss (and 3 inches off the waist) after two years might not even be particularly noticeable in many of them. This drug simply does not take obese people and make them svelte; that\'s not what it does. It helps - but most of the real help appears to be metabolic. The metabolic improvement is very important. But this stuff won\'t make you skinny.