metabolics opposition in trouble

M.D David Kenley mentioned in an email some time ago that Rimonabant had undesirable side effects.

Now others are waking up as well, lol.

From "Rich and Thin" magazine (USA):

The highly anticipated obesity drug from Sanofi-Synthelabo SA SNY: (NYSE ADR) Acomplia (Rimonabant) is a small molecule antagonist of the CB-1 receptor. The "CB" in the receptor name stands for "cannabinoid", and the drug blocks the same receptor whose stimulation causes the well-known food cravings brought on by marijuana. Blockade of this receptor not only seems to affect appetite, but also seems to help with cravings for nicotine.
We had added SNY to our model portfolio based on promising Phase III results that demonstrated Acomplia's efficacy against obesity and nicotine cravings. However, recent disturbing news raising questions about side effect of Acomplia have led us to remove our buy recommendation for SNY.

Most worrisome is that a patient suddenly came down with multiple sclerosis after having been a subject in a rimonabant trial. There's some evidence that CB-1 has a neuroprotective effect under normal conditions. So blocking its actions might conceivably expose neurons to damage.

The MS concern comes on top of a report that Vanderbilt University researchers are expressing concern that the diet drug Acomplia (rimonabant) may potentially increase the risk of ectopic pregnancies in young women, according to a report in the October issue of the journal Nature Medicine.

Ectopic pregnancy occurs when a fertilized egg implants in tissue outside of the uterus, and the placenta and fetus begin to develop there. The most common site is within a fallopian tube. The Vanderbilt researchers, in a study of the CB1 receptor which is targeted by Acomplia, found that in pregnant mice that lacked the gene for the receptor, or in which the receptor was blocked, the embryo failed to go through the oviduct – the tube leading from the ovaries to the uterus.

It is not known whether drugs that block the CB1 receptor can cause ectopic pregnancy in humans. According to the U.S. Centers for Disease Control and Prevention, about 100,000 ectopic pregnancies occur in the United States each year (out of more than 6 million total pregnancies) and account for about 9 percent of all pregnancy-related deaths in the country.

Even though Acomplia has been tested on more than 13,000 people in Phase III trials, if the odds are that 1 in 13,000 that it causes MS, that would probably doom Acomplia. That there is a proposed causation by which Acomplia's action on the nervous system leads to MS and an actual case of MS in an Acomplia trial could preclude FDA approval.

We are contuing our buy recomendations on Lexicon: Genetics (Nasdaq: LEXG) .Metabolic Pharmaceuticals (MBP:AU), Regeneron Pharmaceuticals Inc.(REGN) and CuraGen Corp. (CRGN).

The shares of Metabolic Pharmaceuticals Ltd. an Australian company also trade over the counter in the USA with the symbol MBLPF. They have risen to new highs on anticipation of the results of a Phase IIb study ofMetabolic’s candidate obesity drug, AOD9604, invented at Monash University.It acts specifically on the body’s fat cells to enhance the breakdown of stored fats and inhibit the synthesis of new fat. This result is biochemically similar to the slimming effects of physical exercise.

AOD9604 has proven to be effective in reducing obesity in laboratory animals through once daily oral administration, with no effect on food intake. The drug is modelled on the active fat reducing portion of the human Growth Hormone (hGH) molecule. hGH occurs naturally in the body and is involved in promoting growth. In addition it has pronounced effects on body fat. Scientists at Monash University have shown that, when dosed to animals, AOD9604 has the fat-reducing effects of the intact growth hormone without its other unwanted effects having been observed.

A double-blind Phase IIb study on 300 patients in Australian hospital has been complete and the results are to be announced in November