Close Concerns: Qnexa’s FDA Advisory Outcome

Last week, the influential healthcare information firm Close Concerns published a rather lengthy interview regarding my take on a wide range of issues related to the future of obesity management. The interviews were conducted by Joseph Shivers, Vincent Wu, Lisa Vance, and Kelly Close, who certainly challenged and stimulated my thinking with their well-informed questions.

The following is another excerpt from this interview published in their newsletter Closer Look:

JOSEPH SHIVERS: Thank you so much for agreeing to speak with us, Dr. Sharma. We appreciated having the chance to hear you present at the recent Qnexa advisory committee meeting in April. Some were surprised that the ultimate committee vote was so positive (20-2). What factors do you believe contributed to that vote?

DR. ARYA SHARMA: A couple special circumstances surround Qnexa’s situation. First, because it’s a combination of two drugs that are already generic and are probably already being used off-label by physicians, there is a certain urgency in approving Qnexa which may not exist for other drugs. Without a positive vote for Qnexa, people would just be using the off-label combination because both drugs are available. The problem would be that you then have virtually no control over who’s prescribing it or who’s using it. Even more importantly, you would never have a long-term efficacy or outcome or safety study because nobody would conduct it.

Also, the data, in terms of weight loss, is probably the most convincing we’ve seen from any obesity drug so far. The issues of hypertension, which you’ve seen in previous drugs, clearly do not exist for this drug. There is a very clear blood-pressure-lowering effect. As to the small increase in heart rate – nobody really knows what that means, and most cardiologists would tell you that it’s probably not very relevant, given that the drug has all these positive cardiometabolic effects.

Both circumstances – the fact that you have a very effective drug, and you have a drug that is the best composite of two drugs that are freely available as generics – make Qnexa’s situation special.

The second problem that I think the FDA advisors probably considered, is the fact that the potential teratogenic risk is limited to women of childbearing age that get pregnant. That is an important issue that needs to be considered, and you need to put steps in place to try to minimize it. But it also means that there’s no risk for men, there’s no risk for women who are not of childbearing age, and there’s probably no risk for women who are using contraception or not trying to get pregnant, and it is appropriate to use with these patients.

So, you’ve got a huge section of the indicated population for whom this drug clearly has benefits or is likely to have clear benefits, but nearly zero risk. I won’t say zero risk, but I would say that at least the possible risk of teratogenicity is not relevant to them. Again, we don’t know what that heart-rate risk is; it’s probably minimal, but we don’t know. And so when you have this, your only other alternative would have been to follow what the company had suggested initially, and just make this drug available to men and to women not of childbearing age. That would be unfair to all the women who are not planning to have kids and who are using contraception.

So it’s a unique situation for Qnexa that does not exist for other obesity drugs. If a completely new drug were to come out that is not generic, not on the market, etc., the situation will be different.

So I can, in the end, understand why the panel recommended as strongly as they did. I would not have thought it would be 20-to-2, but I would have been surprised at a negative vote.

JOSEPH: Assuming that Qnexa will be approved – which we do, based on the extended review but absence of a Complete Response Letter (see for our coverage) – how do you think that it will change clinical practice, and over what time period?

DR. SHARMA: Based on the experience on the previous use of drugs for obesity, there’s usually a rush for new drugs, depending on how they’re launched. Usually they launch with quite a bit of fanfare; even if the company is not generating the fanfare, the media is. Often lots of people will try the drug during the first year or so. Given the way it’s going to be dispensed, it will be a prescription, they’ll take it for a couple of weeks, and then some will realize that it’s not working for them or it’s not what they expected or they experience side effects or whatever, and then they’ll stop using it. On the other hand, with a REMS in place for Qnexa, even obtaining a first prescription may not be that easy, and this will certainly further limit uptake.

Repeat prescriptions of obesity drugs have always been rather limited because most people look at obesity drugs as drugs that you take to help you lose weight. But you have to actually keep taking them to keep the weight off. Most people will think, “You know what, I’ll just get the drug, and once I start losing weight I’ll get more active and do what it takes to keep the weight off.” That’s where everybody kids themselves, because that’s not how these drugs work. That’s not how obesity treatments work in general.

So you’ll see in the initial uptake that lots of people want to take a new ‘weight-loss’ drug. Most people that try it generally end up not sticking with it. But I do think that when prescribers and patients learn to handle this drug, and this whole notion of long-term treatment for obesity hopefully gets across, there could be a very substantial market for it. It’s not going to be the multi-billion-dollar drug overnight that most people think you may have, because that’s always been said about every new obesity drug. Then in reality it turns out that the market uptake and development tends to be a lot slower. Especially for this one, if you’re going to have all sorts of obstacles in place to prescriptions, then the uptake might be smaller and slower than you think. But I’m not saying that’s a bad thing.

JOSEPH: We know that reimbursement will ultimately be very important for Qnexa, and we assume that reduction in co-morbidities will help drive that. Can you say broadly how much you think that reimbursement will drive market dynamics, both in the US and in Canada?

DR. SHARMA: Nobody minds paying a couple of hundred bucks for a couple of months to take a drug that’s going to help them lose weight. But then if you tell them, “Once you’ve lost your 5% or 10% body weight you have to keep paying those hundred bucks a month just so that you can keep the weight off, but you’re not going to lose any more weight,” that’s when the reimbursement issue becomes relevant. People have to continue paying whatever it is that they’re paying (it’s usually a hundred or a couple of hundred bucks a month). They’re not losing more weight because they’ve achieved that maximum effect. So they wonder, “Well, why am I still taking this?” Payers traditionally have been extremely reluctant to pay for obesity drugs. My guess is that even with a new drug, you’d need more efficacy for it to be reimbursed—they are not going to be rushing to go forth on wanting to reimburse this: in Canada or the US or anywhere else.

JOSEPH: Do you think that gaining reimbursement is mainly a matter of getting the sort of long-term outcomes data that Vivus is going to be seeking in its long-term cardiovascular outcomes trial?

DR. SHARMA: You have to do a whole bunch of legitimate studies showing that you are actually getting some very real economic benefits of the treatment, and that’s where you get the attention. For example, your diabetes gets much better, or you are preventing a lot of diabetes, or you’re getting enough weight loss to really get people off sleep apnea – whatever it is – through taking this drug. One could argue that Vivus’ two-year extension trial is not large enough and not definitive, but the results all point in the right direction and, if confirmed in larger studies, such results would certainly get payors’ attention.

Edmonton, Alberta

Disclaimer: I have been a paid consultant to Vivus, the maker of Qnexa