when they released their first clinical trial results. Orexigen, based on my recent interview with CEO Mike Narachi, says it doesn’t plan to market its treatment to the masses who are a little bit overweight, but instead wants to pitch it to people who are more seriously obese, and need to lose weight to protect themselves from all the “co-morbidities” of obesity, like diabetes and high cholesterol.
Arena, by contrast, says its safety profile was so clean in the earlier study that it has confidence to market its product to the broader population of people who want to lose weight, Lief says. The drug showed an ability to be used in a broad patient population, help people lose weight fast, keep it off for a year, and improve important secondary measurements of cardiac and metabolic health, Behan says.
Importantly, the earlier study followed patients for two full years to see whether the Arena drug caused any damage to the heart, and didn’t show any serious concerns. This type of aggressive monitoring was required by the FDA, because Arena’s drug is designed to work in a similar way as Wyeth’s fen-phen combination did in the 1990s, before that drug was pulled off the market because it damaged heart valves. The Arena drug was designed to be more specific—to interact with an enzyme in the brain that controls feelings of fullness—without hitting a similar enzyme on the heart that led to the undoing of fen-phen.
Arena has heard the criticism from investors who say the safety looks fine, but the effectiveness isn’t that compelling. Lief took that one head-on when pressed. “We’re not talking about a wimpy drug from an efficacy perspective,” he says.
To buttress his case, he pointed to results from the earlier study that showed two-thirds of patients lost at least 5 percent of their body weight on lorcaserin, more than double the number who did that well in the placebo group. About one-third of patients on lorcaserin lost 10 percent of their body weight, which was triple the rate who achieved that threshold on a placebo, Lief says. Those readings of effectiveness meet one of the important criteria the FDA has said it wants to see from any new obesity drug.
What that shows is that individual patients can respond quite differently to the drug, and since obesity is related to so many genes, the company can’t say for sure which patients are likely to respond or why. When the data is taken all together, the average patient lost 5.8 percent of their body weight on lorcaserin, compared with 2.2 percent weight loss among those on placebo. The FDA likes to see at least 5 percentage points of improvement from an obesity drug, so Arena fell short on that score.
Lief dismissed that as unimportant, saying the FDA only needs to see a drug hit one of the two main effectiveness goals, not both. “No single drug has ever done that reliably,” he says.
Arena is clearly going to hang its hat on safety. The way I heard it, the message boils down to this: it won’t hurt, and it might help. “We’re positioning our drug to be the standard for broad usage,” Lief says. “Most people can benefit from losing some weight.”
And of course, physicians, the FDA, and insurers will look closely at all the secondary measurements of benefit to see if the drug is really worth it. This demanding set of measurements is part of why the drug development process takes a long time and costs so much. Arena obviously hopes these results will be bulletproof, because it’s hard to imagine a do-over for something with such high stakes.
“We’re going to have robust data from more than 7,000 patients. There were no shortcuts,” Lief says.
