Diet Pills & Rising Tides: Orexigen's CEO Explains

Pharmalot: Investors seem to think this is a signal that the other two diet pills, including yours, are likely to be approved. But there’s no guarantee. If anything, there may be less pressure on the agency to do so. Narachi: There’s still some skepticism out there. But now that one has been approved, I actually think some of the skepticism has disappeared. I think it looks like the FDA is going to approve drugs for obesity… But you’re right, (the Belviq approval) is not a guarantee.. It’s just an example. The only guarantee we have is the dispute resolution letter (which Orexigen filed with the FDA after the agency requested a cardiovascular study; read more here).

Pharmalot: What’s the status? Narachi: We have a very clear path to approval that was outlined in a formal dispute resolution process with the FDA. We got a letter from the Office of New Drugs. In addition, we reached a review decision for a Special Protocol Assessment that matched the letter from the OND. We have top to bottom alignment on what it takes to get Contrave approved. And we ‘re executing. We got the protocol, started the study and doing everything we can to enroll fast and get patients, get an interim analysis and have a shortened type 2 resubmission review, a six- month review.

Pharmalot: Can you review the requirements? Narachi: We’re required to measure, in a large study, the frequency of heart attacks, stroke and cardiovascular deaths in a placebo arm and a Contrave arm and show there’s no doubling of risk – no more than 40 percent risk in a final analysis. But positive results on the interim analysis would yield approval. It’s an event-driven trial. We need 87 events in our trial. Our hypotheses would be the same in each arm… and by chance, it could be a little higher or lower than equal. We unblind after collecting 87 events, and the number of events cannot be worse than 49 on Contrave and 37 on placebo. That’s the worst it can be and still get approved. Our hypothesis is in short duration that they would be about the same in each arm.

Pharmalot: You need 10,000 people, right? Narachi: The sample size targeted for the final analysis is about 10,000 and for the interim is about 7,000. Of course, more patients means the trial goes faster, but costs more.

Pharmalot: And what is the cost? Narachi: To get to the interim phase, the trial will cost about $100 million, somewhere a little bit less than that. And we ended last year with about $138 million in cash. So we have enough cash to get us through the enrollment, the collection of 87 events and resubmission and approval, all of which should happen within two years of starting the study. It started June 1.

Pharmalot: Of course, by then, you’re two years behind the competition. Why should anyone care? Narachi: This is a point of view that a lot of people have held. Every large category of drugs has had many different drugs that act in different ways in terms of mechanisms. Let me give you an example. In hypertension, there are eight different major mechanisms and multiple drugs in each mechanism. It’s the same with cholesterol and diabetes. Pretty rare where you have a large category and there’s only one or two drugs... So, yes, it takes a lot of muscle and promotion to change perception and use pattern with whatever modality. (EDITOR'S NOTE: Contrave combines two older drugs – the Wellbutrin antidepressant and a sustained release form of naltrexone, an opioid blocker used to treat addictions to alcohol and painkillers, as well as curbing appetites. About five four of 10 patients - or more specifically, 53 percent - taking Contrave for a year lost at least 5 percent of their weight, an outcome that just met FDA guidelines for effectiveness).

This market needs to be built and grow. The game isn’t to get a dominant share of the current market. That would be relatively uninteresting. Everyone’s trying to participate in growth of the market. We forecast a much higher level of sales if there are two or three drugs in the market with promotional resources - advertising, education, sales reps - not a lower level. To be alone is okay, but we would get a dominant share of a smaller market.

Pharmalot: The rising tide theory, but being first is still better. Narachi: Would I prefer be first? Yes, it would be better. However, I would also want to contrast that these are different drugs – both on safety and efficacy and comfort that physicians will have. It may take Arena four to six months until it’s done with the DEA (Belviq will be listed as a controlled substance, but final listing has not yet been determined). The good news for them is they have a commercial partner, Eisai. So do we. We have Takeda, which has a much larger US presence and quite a history of building blockbuster brands. Between approval and launch, Takeda would pay $100 million in milestones... and later, other cash flows kick in… We’re in the process of finding a partner for the rest of the world. That would be another source of cash…

Pharmalot: And Vivus doesn’t… Narachi: Vivus (which hopes to win approval for its Qnexa pill next month) is a little different. They don’t yet have a partner and so, there are a limited number of resources... And it appears from the latest advisory panel that approval could come with severe restrictions – elements of safe use – which is a restrictive form of a REMS program... (read more here). So we believe we would have the most competitive profile of any of the drugs... Belviq has not been studied in patients with cardiovascular risk (Arena must conduct cardiovascular studies as part of its approval) We would launch with that comfort, that it passed a hurdle. It’s kind of a good housekeeping seal of approval on safety.

So I think Contrave will be preferred for large portions of the market. If we speculate that Qnexa (which combines the active ingredient in the Topamax seizure med and phentermine, which is the surviving half of the fen-phen diet cocktail) will have an elements of safe use around birth defects, that’s a concern for women of child bearing potential. (EDITOR’S NOTE: If approved, Qnexa would be contraindicated for women of childbearing age over teratogenic concerns). About 80 percent of the market is women and the vast majority are women of child bearing potential. If you have a drug with lots of restrictions on use for that segment, you’ll miss a large part of the market…