Pfizer Also Halts its CB-1 Program for Obesity

Really no surprise here. After first Merck stopped the development of its CB-1 antagonist taranabant and earlier this week, Sanofi-Aventis abandoned further development of rimonabant , Pfizer yesterday announced, that they too had now discontinued the development of their CB-1 antagonist CP-945,598.

Not that these drugs were not effective for obesity treatment. In fact all three compounds were as, if not more, effective for weight loss as the prescription drugs currently on the market. Not only had they been tested in some of the largest randomized controlled trials ever to be conducted in the field of obesity, but they had clearly demonstrated positive effects on lipids, glucose homeostasis, and even blood pressure.

Alas, these positive effects were clouded by a significantly higher rate of anxiety, depression and dysphoria – in the worst cases, even suicidal ideation.

Not that these drugs were actually killing people, but clearly, if widely used (as any obesity drug is bound to be), it would have only been a matter of time before someone somewhere on one of these drugs may have put a gun to his head or jumped off a bridge.

Unfortunately, I do not ever foresee an effective drug for obesity that will be completely without risk. In fact, most drugs (even aspirin or paracetamol) have risks and, in rare cases, can kill you.

It is not about having drugs that are absolutely safe – it is about having effective drugs that are safer than the condition that you are trying to treat: we call that risk/benefit ratio.

In fact, everyday in clinical practice we decide (often simply using our best clinical judgement) whether the risk of treating exceeds the risk of not treating a condition. We happily use lethal poisons to treat cancer, because the risk of using these poisons is statistically lower than letting the cancer run its course.

Obesity is also a condition that kills – that is why, for patients with severe obesity we increasingly recommend surgery, which, even under the best circumstances, on average kills 1 in every 500 to 1000 patients who get it. Despite this risk – most people with severe obesity would opt for (and all guidelines recommend) surgery, because the risk of dying without surgery is statistically greater than the risk of dying from surgery.

With the withdrawal of CB-1 antagonist, patients battling obesity have lost an important option. Given our lack of effective treatments, many will eventually go on to develop more severe obesity and will eventually either succumb to complications from their obesity (heart attacks, disability, cancer) or have to undergo obesity surgery, thereby exposing themselves to a far greater statistical risk than ever posed by taking a CB-1 antagonist.

If obesity drugs are to be used for cosmetic weight loss – no level of risk is acceptable. When used to treat excess weight that threatens or affects health (my definition of obesity), I am certain that there is a significant subgroup of individuals with obesity, who would have benefited from these compounds – these patients no longer have that option.

If the only obesity drugs that will ever make it to market are those that will work for all patients and are 100% safe, we may as well abandon obesity drug development (as Pfizer has decided to do) and work on drastically expanding our surgical programs.

As obesity drugs will likely always be safer than surgery (now the gold-standard for severe obesity), perhaps this is the standard against which future obesity drugs should be measured – their ability to prevent or significantly delay the future need for surgery when used early in the course of this chronic and progressive disease. The safety of obesity drugs would then have to be measured against the safety of surgery – my guess is that even CB-1 antagonists would have passed that test.

Edmonton, Alberta

DISCLAIMER: I have received consultation honoraria and research support from makers of CB-1 antagonists including Merck, Sanofi-Aventis and Pfizer.