Obviously, what the market is very concerned about is the significance of the recent development and regulatory approval of the first new wave of anti-obesity drugs after about 13 years. Now, I wonder if you could give me an idea of what some of the greatest challenges that Orexigen faces in the development of Contrave – your new product – from a scientific and clinical perspective and maybe some of the ways that you’ve met those challenges.
Dr. Klassen: First of all, I’d simply point out that the approval of obesity therapeutics that were developed by the companies Arena and Vivus represent really a watershed in clinical and regulatory landscape in obesity. Just as you’ve pointed out, it’s been 13 plus years since any new therapy has come on the market. For the last several years the concern I think, really, among the community of patients and healthcare providers who deal with obesity was a concern as to whether the FDA really was going to be able to approve therapies in obesity. So, the roadmap and the hurdles appear to be not as clear as perhaps it needed to be. So, a lot of that is getting clarified now. Orexigen has been through that process, along with Arena and Vivus, and we still have a few steps to go through that process. But, we have a path with the FDA that is crystal clear, it’s feasible and it’s one that we are executing on. So, I think again, for the space in general to have new therapeutics available is frankly a watershed moment. It’s good for everybody and we certainly congratulate those other two companies as we move forward with our own compound and hopefully approval in the next short bit of time.
Then you also asked “What are the challenges that a company faces?” I think that each of the three companies – Orexigen, Vivus and Arena – have had their own unique challenges to deal with. But what has been common to all of them, I think, is needing the challenge of appropriate training of risk and benefit in the context of obesity and helping the Agency work through how to think about that. In our compound, Contrave is a great example of what I mean by that difficulty. So, our compound is a combination of two agents that are already approved and on the market today and they have been on the market for the last 25 years. Tens of millions of individuals in the case of bupropion have taken these drugs. So, it’s a combination of bupropion and naltrexone.
Bupropion is a widely prescribed therapeutic. Seven million people take it every year for major depression, seasonal types of disorders and smoking cessation. The theoretical risk that we are currently ruling out with a cardiovascular outcomes trial, some of which occurs before approval, the majority of which occurs after approval in terms of the conduct of that study is needed, in part, or in totality really because of the theoretical risk of bupropion and its impact on blood pressure and heart health. So, that risk/benefit has been deemed for the last 25 years, but theoretical risk, which is no different for Contrave than it is for bupropion because the hemodynamic impact of Contrave is that of bupropion. That risk/benefit has been deemed appropriate for the last 25 years in a variety of other indications. But in obesity, for some reason, it’s viewed differently. So, at least in our specific case, the challenge hasn’t really been so much around understanding risk better, it’s been around how to put appropriate context around the benefits of weight loss. That’s really the challenge – designing phase two and phase three trials, examining clinical weight loss in the appropriate markers that go along with that, cardio metabolic parameters, etc.
That is, frankly, the easy part. The more difficult part is understanding the broader context of obesity and how much risk, how much benefit and putting that together. That’s at least what we faced for the last several years at the Agency. But again, I clearly believe that we’ve reached a bit of a turning point and I think the future looks very bright at least for therapeutics.
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