Friday, August 13, 2010

CRESCENDO, rimonabant's "obituary," published in Lancet

I thought that I should close the chapter on Rimanobant nicely, just as my US colleagues did.
We will all recalled rimanobant, hailed at the turn of the millenium as a breakthrough drug for the then " in fashion " cardio-metabolic syndrome. Rimanobant belonged to a new group of drugs called the Endocannabinoid receptor blocker. Endo-cannabinoid comes from the word cannabis, meaning that this new group of drugs attacks a cannabis-like receptor that in the brain, to cause one to not feel hunger, not eat so much, therefore lose weight and help correct all the downsides of obesity, like diabetes and hypertension and prevent heart disease. It sounded so good. Almot too good to be true. It was hailed as a block-buster drug. There were many large scale studies done, led by some very prominent cardiologist, to show that it could help patients lose weight, have less hypertension, and diabetes, and so less heart disease.
I remember being invited to the local launch for this new block-buster drug. Even before the launch, I had already given my imput ( privately ) to the local MNC pharma boss that this drug was trouble, and not to worse too much money on it. Of course, our coloured skin opinion was largely ignored as the MNC had to listen to their head office in faraway land. The launch was a bid affair, with speeches, and dinner ( I think ). We again, registered our reservations ( in a gentle, unobtrusive way ).
Our reasoning was simple ( I am no great research worker, not in clinical private practice anyway ). Cannabis make us want to fly like a bird. If you block the cannabis like receptor, it will make us sink like a stone. I warned that I see neuro-psychiatric side effects as a big problem. Obesity itself may have a neuro-psychiatric component.
Sad to say, our fears were proven right. In 2008, the European drug authority removed the drug from Europe, because of reports of suicides and depression. The large clinical trial " CRESCENDO ) which were enrolling patients then were told to stop the study. The authors protested, that it was important to establish if Rimanobant does help to lose weight and lessen cardiac disease. The authorities allowed the study to go on, but the doctors were fearly to recruit patients. Basically, the study was halted.
Anyway, after 14 months of followup and two years later, the CRESCENDO results were published in the Lancet, 14th August. Please remember that it was a shortened study and enrollment was incomplete. It showed that rimanobant did not better then placebo, in terms of CV mortality and morbidity. There were however 4 suicides in the rimanobant arm, and 1 in the placebo arm. There were also more attempted suicides ( 9 ) in the rimanobant arm and less ( 5 ) in the placebo arm. There were more depresions and anxiety discorders in the treatment arm. Basically, the authorities were right in withdrawing the drug.
I felt very bad that I loss a patient and friend who was on rimanobant. He was obesed with diabetes, hypertension and established heart disease ( I had done a triple vessel angioplasty ). I gave him rimanobant to help him lose weight. This was before the ban and withdrawal of rimanobant. He did well. The sugar / BP control was better and he lost weight. When the Ministry of Health advised that rimanobant should be withdrawn, I told him and asked him to stop taking. He decided that he wished to continue. I gave him whatever stock I have left. A month or so later, I was told that he had gone on an out-station business trip alone and was found dead in his hotel room. There was no suicide note and he was not depressed before the trip. When I heard that, I felt so bad. I will never know whether the rimanobant contributed, in anyway to his death, or was it just sudden cardiac death.
Well, now we can close the chapter on rimanobant. The pharma developing the drug, must have lost millions of dollars, on an unfulfilled dream.
It was good that CRESCENDO was completed ( in a way ). We now have scientific facts to support our opinion. It is always sad that for progress, some had to die on the way. We only hope that they did not die in vain.

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