With rise obesity around the world there should have been a number of drugs to combat it. The reality is different. There are no safe and effective drugs in the market at present.
Now one drug that had faltered in the pipeline – Orexigen Therapeutics’ Contrave - - just got a new lease on life after being rejected for approval by the Food and Drug Administration in February. The FDA informed the company Tuesday that it will reconsider Contrave for approval if a clinical trial removes any concern about risks to the heart. The company said in a statement that the FDA’s requirements are “reasonable and feasible” and it plans to go ahead with the trial, which will take several years.
Contrave is a mixture of two medications, naltrexone and bupropion. Both are already on the market. Bupropion is the active ingredient of the antidepressant Wellbutrin and the anti-smoking aid Zyban. It increases the available levels of three key chemicals in the brain: dopamine, serotonin and norepinephrine. Naltrexone blocks the receptors in the brain that opiate drugs attach to, and it’s used to treat people with addictions to heroin and other opiates. It’s also used to treat alcoholism. The two drugs were combined as a weight-loss tool because bupropion increases the activity of key neurons in the brain (called POMC neurons), thus causing appetite to diminish and metabolism to rev up. Naltrexone was added to block a certain natural brain opioid that gets in the way of this stimulation.
Clinical trials showed that 50% of people taking the drug were able to lose 5% of their body weight over a year, compared with only 10% in a group that got a placebo or dummy. Based on this, in December, an advisory panel recommended that the drug combo be approved for treating obesity, as long as possible heart effects were closely tracked afterward.
But the FDA decided to reject Contrave because many people experienced slight increases in blood pressure or pulse rates. Because part of the reason to get people to lose weight is to help fight heart risks, negative effects such as these would seem to cancel out the gains.
Orexigen, whose shares jumped 87 percent in after-hours trading, now says Contrave could be approved as early as 2014. The 2014 date seems a little over-optimistic (the heart study won’t start until the first half of next year), but the news for Orexigen really is positive. The clinical trial will still be huge, with as many as 10,000 patients. And it will be expensive. On a conference call last night, Preston Klussen, Orexigen’s head of development, said that similar trials cost $10,000 to $12,000 per patient. That would be a $100 million trial. That’s more than the $70 million Orexigen has in the ban. Even with marketing partner Takeda chipping in. Orexigen will need to raise money.
The FDA told Orexigen, in writing, that “if the interim analysis meets the specified criteria to exclude an unacceptable increased cardiovascular (CV) risk, the drug could be approved.” That “could” is pretty important — the FDA might consider the results of such a trial and decide that Orexigen’s risks still don’t outweigh its benefits. The FDA also said that its upcoming advisory meeting on the regulatory hurdles for obesity drugs won’t change the requirements for this study.