When Addyi, the first prescription treatment to enhance sexual desire in women, was approved back in August it was dubbed “the female Viagra.” Valeant Pharmaceuticals quickly scooped up the drug’s manufacturer, Sprout Pharmaceuticals, for the tidy sum of about $1 billion, and the hype about how well Addyi would sell began to flow. But the results have not lived up to the hype.
In December, healthcare industry analyst Symphony Health Solutions reported that 1,841 prescriptions for Addyi were filled in its first 10 weeks on the U.S. market. Back in 1998, Viagra filled more than 500,000 prescriptions in its first month alone. Of course, the comparison between the two drugs is actually quite minimal.
Addyi is approved to treat premenopausal women with hypoactive sexual desire disorder, or HSDD, a libido-diminishing condition that affects up to 10% of U.S. women. Addyi is also a daily pill that has to be taken every night, compared to Viagra, an erectile dysfunction treatment, which can be taken as needed. Another barrier to getting an Addyi prescription is just finding a doctor who is able to prescribe it. Doctors must first take a 15-minute online training course from the FDA to be certified to counsel patients not to drink alcohol before they can write a prescription for Addyi. In late December, Valeant announced that about 7,000 prescriptions have been held back due to lack of FDA required certifications.
Still, that is a far cry from the lofty expectations some predicted for Addyi. PM360 recently spoke to Nick Sitchon, CEO of S1 Biopharma, a company currently developing its own treatment for HSDD called Lorexys. Sitchon offers his thoughts on Addyi’s slow start and why he believes Lorexys is better positioned for success.
PM360: Why do you think Addyi sales have been so slow out of the gate?
Nick Sitchon: There are a number of reasons for the slow start of Addyi (flibanserin), starting with the fact that some severe restrictions were put on the prescribers by the FDA as a condition of the drug’s approval. In addition to doctors requiring certification, pharmacists also do. Having both available to one patient adds exponential complication. Addyi sales will probably get better with time, since few of either had time to get certified yet.
Also, based on clinical data and the literature—both the New England Journal of Medicine and JAMA—it’s really not that much of a surprise. Studies have shown flibanserin had a maximum efficacy rate of between 10% and 15% over their control, and had questions about its benefit to risk ratio.
However there is a huge unmet medical need. It’s a $5 billion market due to its prevalence: 1 in 10 women in the Western world. It is a market that will be served by the first drug that has very good efficacy and tolerability and acts as a restorative treatment, rather than just as a mild aid.
What makes Lorexys different from Addyi and do you to believe it will have greater success in the market?
Lorexys is the brainchild of the inventor of flibanserin, Dr. Robert Pyke, who was also the head of the clinical program that developed flibanserin at Boehringer Ingelheim before the asset was divested to Sprout.
Dr. Pyke is now our Chief Medical Officer and Co-founder of S1 Biopharma, and the co-inventor of Lorexys—which is a very different drug from flibanserin. Ours is a dual control mechanism of action, so it’s comprised of two different drugs, bupropion and trazodone. Bupropion has a stimulating effect. Trazodone has a sedative effect. And we have created a proprietary fixed dose combination so that the unwanted stimulant effects of the bupropion and the unwanted sedative effects of trazodone are offset to a perceived cancellation of side effects to the patient.
Sort of like hot water/cold water—when you have the right amount of each, it’s very comfortable. But what we found in early pilot study data is the pro-sexual benefit is not cancelled or balanced out. It’s augmented in a synergy. So whereas trazodone has very little to no pro-sexual benefit, and bupropion has some very modest pro-sexual benefit, when combined together in this fixed dose combination, we see a 76% responder rate and a 58% remission rate.
What that means is the patients who enter the trial, within four weeks, 58% of them left the trial with no more HSDD. And these were the most severe patients by the entry criteria with some patients having HSDD for five to 10 years.
You mentioned some of the restrictions on Addyi. One thing you did not point out were some of the reported side effects such as low blood pressure, fainting and the fact that you can’t drink alcohol with it. Will Lorexys have any of the same restrictions or any side effects not seen with Addyi?
The one major thing that I would highlight is that we do not anticipate any big counter-indication or a restriction against alcohol. Of course, the FDA can determine whatever they wish, so it may ultimately have some restriction but we don’t know what the outcome will be at this time. But so far, our drug has very good tolerability.
Is it still a daily pill?
Yes, it’s a pill taken once daily, just before bed.
I think that is an important distinction when comparing the sales of Viagra and Addyi, because with Addyi you have to build up the effectiveness of the drug over time. It’s not something you can just take right before you want to have sex. I was wondering if you think that could also be an impediment for Lorexys?
That’s a really interesting question. HSDD is very different from erectile dysfunction—HSDD is essentially defined as a distressing lack of desire. It occurs in both men and women, and we are actually developing a male HSDD drug as well called Orexa.
But for women, the prototypical HSDD patient is somebody who had a very healthy libido and then it’s gone suddenly. There is this sense to patients with HSDD that they’ve lost something very personal to them. So it’s not so much about having sex on the spot or having intimate relations in the moment, as much as it is just feeling restored to what they formerly considered normal.
Those who have studied HSDD over the years have learned that women want their desire restored all the time. Those who are seeking relief from having HSDD aren’t seeking to have sex in the moment. It’s almost a psychiatric and personal feeling rather than a sexual disorder.
Adherence also becomes an issue when pills are taken daily. Do you have any adherence programs planned for the time of launch to help patients stick to treatment?
It’s a little early for us to be promoting our plan, but in conjunction with our scientific advisory board, and under the guidance of Dr. Robert Pyke, we plan on having a hand-in-hand treatment regimen and educational structure as we work closely with potential prescribers. Because the most successful HSDD treatment will be one that is coupled with talk therapy and close supervision with your prescriber.
I know you said it is a little early to talk launch plans, but when Sprout originally launched Addyi, they said that they would hold back on DTC advertising for 18 months. Do you plan to take a similar approach, or do you want to get the message out to patients?
The DTC restriction was put on flibanserin for various reasons, including its tolerability effects. It is our hope that because our tolerability so far in Phase II has been what we would consider excellent—we had zero dropouts at all due to sedative effects or any of the effects that are typically associated with the drug—so we hope and expect that we will not be subject to the same restrictions.
What about the restriction the FDA put on Addyi prescribers and the need for the online certification? Do you anticipate any restrictions in that regard?
If I were to guess, I would guess “no” based on my understanding of the restrictions being put in place due to the tolerability profile of flibanserin. But you never know. Certainly I don’t think our drug would warrant or deserve something that extreme because our tolerability is so far very good, and we hope to further demonstrate that in Phase IIb and Phase III.
Did you learn anything else from Addyi’s launch that may change how you would approach yours differently once you get there?
One of the big questions that has been looming over the past decade about HSDD is what are the criteria for FDA approval? And now that Addyi has successfully been approved by the FDA, we know the benchmark for future approvals. Typically in CNS, in order to be competitive for FDA approval, generally, it’s about a 20% efficacy over placebo. Addyi achieved FDA approval for almost half that, simply because the need for a treatment for HSDD is just that significant.
Valeant bought Sprout quickly after Addyi was approved. Would you be interested in either a merger or just a partnership with a Big Pharma company as you get closer to launch?
Most certainly, we have a small handful of ongoing, long-term relationships with Big Pharma. Our intention is to license the drug. We do have an on-the-shelf option to sell it ourselves, but we received a lot of interest already. We’ve had overtures to license Orexa already, the male drug. So yes, that is the most likely outcome, wherein we would license or partner with large pharma, with a field force that was able to maximize the potential of Lorexys. Drugs like Lorexys don’t grow on trees, and we really want to make sure that the partner is capable of maximizing its reach to the patients who need it.
Is there as big of an unmet need for the male HSDD drug?
That is something that may surprise your readers. The answer, no doubt about it, is yes. In the KOL community, the belief and understanding is that erectile dysfunction only has less than a 50% re-prescribe rate. And it’s believed that it’s because those who think they have ED may actually have a lack of desire. So you may have some desire, but not enough desire to get you over the threshold for being normal for HSDD. So we believe that the market for HSDD is equivalent of the market of erectile dysfunction—maybe even greater.
But do you think you would have marketing challenges with a male HSDD drug? Some patients don’t even like to admit they suffer from ED. Do you anticipate any issues with the ability to reach male HSDD sufferers?
There’s a great deal of interest in male HSDD. Before ’98, nobody wanted to admit that they had an issue achieving an erection. But, $5 billion per year later it was proven differently. And I don’t think this is any different from that.
So you’re planning on taking a minimal marketing approach then?
Yes, absolutely. We’re here to serve a need, and if patients need it, they’ll seek us out.