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After Orexigen Gaffe, What Role for Drugs Amid Obesity Crisis?

Xconomy National — 

Two recent happenings prompted this column. First, Orexigen Therapeutics drew fire from, well, nearly everyone earlier this month for an improper release of data related to its weight-loss drug Contrave. The second happening is Memorial Day weekend.

I’m assuming you, like me, did not spend the long weekend hunting and gathering, sharpening your arrowheads, and ranging far for firewood.

But that’s what our bodies still expect us to do, and they plan accordingly, storing as much energy as possible in our cells. “Humans are one of the few species who eat when we’re sad, happy, angry, even when we’re sick,” says Kevin Grove, an obesity expert at Oregon Health & Science University in Portland who was recently tapped to run Novo Nordisk’s obesity R&D group in Seattle. “It’s that secure feeling we get from various foods, whether it’s chocolate cake or a big steak.”

Our ancestors never knew when the next meal was coming. Now, the next meal is just a weekend barbecue or online delivery away, and it’s often filled with the fats and sugars we’ve evolved to crave but no longer have the lifestyle to burn off.

Which brings us to Contrave from San Diego-based Orexigen (NASDAQ: OREX). The drug is actually a combination of naltrexone, a substance-abuse deterrent, and buproprion, an anti-depressant, and it’s one of only four products approved for obesity in the U.S. They generally work by suppressing appetite, and all are combinations (like Contrave) or reformulations of older drugs (like Novo Nordisk’s Saxenda, a higher-dose version of Novo’s approved diabetes drug liraglutide).

In other words, faced with a full-blown epidemic—35 percent of adults and 17 percent of children in the U.S. are obese, according to the latest figures from the Centers for Disease Control—doctors don’t have a lot of pharmaceuticals to prescribe.

Now both Orexigen and Contrave are under a dark cloud. After four years of regulatory pinball, the FDA approved the drug in September 2014 under special conditions. Among other things, Orexigen has to keep testing it for long-term cardiovascular side effects. It’s that work that has the company in hot water.

“It’s the latest in a series of—I won’t exactly say ‘failures’—but certainly problems coming up with drugs to treat obesity,” says Rick Hecht, director of research at the Osher Center for Integrative Medicine at the University of California, San Francisco.

In March, Orexigen filed a patent application that disclosed 25 percent of the heart study data and touted a purportedly positive benefit of Contrave in preventing heart attacks. But that ill-timed release, against the wishes of the academics running the trial, backfired. The FDA now says the trial is tainted; Orexigen has said it will do it again from scratch; and its R&D partner, Takeda Pharmaceutical, wants Orexigen to pay the entire bill—potentially hundreds of millions of dollars. What’s more, further testing that produced another 25 percent of the data reduced the positive cardio effect to neutral, according to a statement from Steven Nissen, the Cleveland Clinic cardiologist running the trial.

The Contrave situation could exacerbate what’s already a tepid response to the latest obesity drugs. “Doctors aren’t prescribing them,” says Edmund Pezalla, national medical director, pharmacy policy and strategy of the insurance giant Aetna. “It’s been a really slow uptake.”

The latest numbers compiled by RBC Capital Markets biotech analyst Simos Simeonidis show that the four big brand-name drugs have leveled off at roughly 30,000-to-35,000 prescriptions a week recently.

That’s about double the rate from the end of 2014, and if sustained for a full year would account for up to 1.8 million prescriptions. But here’s an interesting point of comparison: One study showed that in 2011, before any of the new drugs were approved, 2.74 million Americans were prescribed anti-obesity drugs. Assuming some of those Americans received more than one prescription that year, the current crop of drugs have a lot of catching up to do. (It’s also worth noting that most of those Americans in 2011 were being prescribed phentermine, one component of the notorious “fen-phen” combination that was taken off the market in 1997 after multiple deaths. The other component, fenfluramine, not phentermine, was the culprit).

Pezalla says that although the average weight loss for each drug is different, there’s a lot of overlap among patients, and no way of knowing prior to taking the drugs how effective they’ll be. It’s not just doctors who are reticent; Pezalla also notes that 85 percent of Aetna members are in plans that don’t cover weight-loss drugs.

Drugs have done tremendous things to fight some diseases in some parts of the world: turning HIV infection in developed countries from a death sentence into practically a chronic condition, for example. But they’ve done little good in other areas, including obesity. Why should we pin our hopes on pharma to melt away our societal fat?

Losing the war on obesity means a host of other complications for millions of Americans like diabetes, heart disease, hypertension, sleep disorders, and on and on. (The CDC estimates 86 million Americans over the age of 20 are in danger of turning diabetic.) A study last fall suggested obesity rates have stabilized—a tiny glimmer of good news—presumably with little to no help from pharmaceutical interventions.

But it seems drugs will have to be at least part of the solution, especially for the severely … Next Page »

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