) caused a stir when it unveiled data on a promising experimental drug for obesity. The drug, rimonabant, seems to stem cravings in humans, thus reducing obese patients' appetites. If it proves safe and effective, rimonabant could see peak annual sales of $3.6 billion, says Jean-Francois Dehecq, the pharmaceutical company's CEO.
Few treatments for obesity have garnered as much excitement in recent years. The existing prescription drugs got attention when they were introduced several years ago, but that has faded amid some less than favorable publicity. The two approved for use in the U.S. -- Roche's Xenical and Abbott Labs' (ABT
) Meridia -- both offer modest weight loss and unpleasant side effects. A drug that produced significant weight loss, Wyeth's (WYE
) Redux, was removed from the U.S. market in 1997 after being linked to a deadly heart condition in some patients.
"GUT FEELING." Indeed, the market is ripe for better options, considering obesity (defined as being 30% or more over ideal body weight) affects a third of the U.S. population and will soon pass smoking as the No. 1 preventable cause of death. (In fact, rimonabant also seems to be effective in helping smokers kick the habit, and Sanofi is studying it in separate trials for smoking cessation as well.)
Rimonabant could prove to be the first bona fide success in years. It's the most advanced of any anti-obesity drug in testing and so far, preliminary data from large studies have shown that weight loss is more dramatic than with existing drugs. Four trials for the drug as an obesity treatment are ongoing. Rimonabant works by blocking receptors of a substance called cannabinoid 1, which stimulates hunger and other cravings in the brain and is also present in fat tissue.
"Really, my gut feeling was that we will block this receptor, and the body will compensate, but it was not the case," says Dr. Jean-Pierre Despres of Laval University in Quebec City. Dr. Despres led a trial of rimonabant in 1,036 overweight patients at high risk for heart problems. All patients were told to cut their food intake by 600 calories daily. Those who received a 20-mg dose lost an average of 20 pounds and trimmed their waistlines by three inches in one year. Those given placebos lost an average of five pounds.
DUAL PURPOSE. Rimonabant could have more, well, heft behind it, than predecessor treatments, which focused primarily on weight loss. Sanofi will try to hold its drug up to doctors and insurers as a product with the ability to cut cardiovascular risk factors because of its effect on cholesterol levels. "We don't view this as an 'obesity drug,'" says Dr. Douglas Greene, vice-president for corporate medical and regulatory affairs at Sanofi. "It has therapeutic potential to impact a major public-health problem -- the growing epidemic of cardiovascular risk."
Patients in Despres' study saw their levels of HDL cholesterol, the good kind, rise 23% on average, while triglycerides, a kind of cholesterol that is beneficial at lower levels, fell 15%. Rimonabant appears to alter the level of cannabonoid 1 in fat cells, which could be one way that it affects cholesterol concentration, Despres says. Sanofi will reveal more data throughout the year and says it hopes to file an application to the Food & Drug Administration in early 2005. The drug could be on the market as early as 2006.
If approved, rimonabant won't have much competition. A look at drug and biotech companies' pipelines reveals few projects in broad human studies. Only one other treatment is in Phase III testing, Axokine, made by Regeneron (REGN
). But that company has been quiet about Axokine's status since patients seem to develop resistance to it over time, says Dr. Eleftheria Maratos-Flier, head of obesity research at Joslin Diabetes Center in Boston.
"If people take this and have to stop [because resistance develops over time], what would be the point?" she wonders. Plus, Axokine, as a biotech drug would be pricey, and it would require an injection -- two more strikes against it.
NO REDUX REDUX. Earlier-stage anti-obesity drugs encompass a myriad of approaches, suggesting that the science of obesity is complex and not well understood. "It's a very difficult area," says Ginger Johnson, senior consultant at Defined Health, a pharmaceutical strategy consulting firm. "But drug companies won't give up. The market is just too big."
Just as drugs to treat depression did in the 1990s, the first safe and effective anti-obesity drug would spark massive demand, says Johnson. Bernstein Research analyst Gbola Amusa figures that rimonabant could be a $541 million drug in 2008.
Just because the coast is clear in terms of competition doesn't mean rimonabant won't face other challenges. "There are multiple levels of problems" with anti-obesity drugs, says Mark Ravera, senior consultant at Defined Health. Safe weight loss is slow, and even with drugs that expedite the process, obese patients, who may need to lose much more than 20 pounds, can become discouraged quickly and drop treatment.
SIDE-EFFECT QUESTIONS. Also, depression often accompanies obesity, but it's hard to say whether depression is at the root of overeating or the other way around. "[Curing obesity] is not a simple medical change, as with many other diseases," Ravera says.
Side effects have plagued other anti-obesity drugs, and rimonabant won't be an exception. In the obesity trial, it caused nausea in 13% of patients, vs. in 4% of those who got placebo. Anxiety and diarrhea also occurred at a higher rate in patients taking rimonabant than in placebo cases. Sanofi will need to show that its side effects are limited and short-lived, and that longer-term use won't reveal more serious problems like the ones seen with Redux, a.k.a. fen-phen.
Still, physicians are hopeful that rimonabant will join the relatively weak arsenal they have to combat obesity. Maratos-Flier says her patients "almost never" reach their weight-reduction goals. The most effective method, in many cases, is gastric bypass surgery. "[Rimonabant] is definitely a potential improvement," says Maratos-Flier, particularly if it's a once-daily pill that patients could stick with. "If it can help obese patient lose 20 pounds and stabilize that weight loss, I would keep them on the drug."
Of course, preventing obesity by changing eating habits should still be the highest priority, says Maratos-Flier. That kind of societal change will take decades, so it makes sense that other options are under serious consideration -- and are being seriously sought. While researchers are quick to caution that rimonabant won't likely be a silver bullet, it could be a more viable option in treating obesity and its related health problems. Tsao covers biotechnology issues for BusinessWeek Online. Follow her Biotech Beat column only on BusinessWeek Online