The approval of Sprout Pharma’s Addyi (flibanserin 100 mg) is emerging as one of the most significant biopharma stories of 2015. Addyi has managed to touch a collective nerve that speaks to the pent-up demand for a women’s libido-enhancing drug, but also our societal anxiety about female sexuality in general. Those issues notwithstanding, some experienced biopharma marketers predict robust uptake in a fairly short period of time.
Just two days after Addyi was approved, Valeant announced its $1 billion acquisition of Sprout, which will provide significant marketing muscle for Addyi, as well as the opportunity to commercialize it globally. The assumption is that the demand is there—not only in the U.S., but in other countries as well.
According to a survey from Treato, a "big data" company that aggregates patient experiences from the Internet and organizes them into usable insights, 80% of surveyed women said they would take a daily pill to improve low sex drive. So there is clearly a market for a female libido-enhancing treatment. But many experts are concerned about the side effect profile associated with Addyi.
The pros and the cons
On the upside, Addyi is approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Addyi is an oral, non-hormonal drug, which fills a longstanding unmet medical need. It is the first FDA-approved drug for the treatment of sexual desire disorders in men or women.
It also has the support of powerful women’s groups: A coalition of advocates called "Even the Score" rallied hard for Addyi—even after the FDA rejected it twice, first in 2010 and then again in 2013. And now Addyi has become a touchstone—a conversation starter about women’s sexual well-being. In many ways, the approval of Addyi is a major milestone for women’s sexual health despite what critics have called its modest effect.
On the downside, Addyi comes with a black box warning highlighting the risks of severe hypotension and syncope (fainting) in patients who drink alcohol. In fact, the label recommends bedtime dosing to help reduce the risk of adverse events associated with drug-related hyptension, syncope, and central nervous system (CNS) depression. There is also a risk of accidental injuries—an event that 2.7% of Addyi-treated women experienced in clinical trials.
In addition, the FDA attached a Risk Evaluation and Mitigation Strategy (REMS) to Addyi, which requires that healthcare providers and pharmacists watch an online slide presentation and take a test before they can prescribe or dispense it.
Are women willing to give up alcohol?
Eric Malter, Founding Partner and CEO of MDC, a programmatic healthcare advertising and communications agency in New York City, has 40 years of pharma marketing experience, including with numerous women’s health products such as Premarin and the Today Sponge. He has some reservations about how well patients will comply with their physicians’ instructions and warnings about Addyi.
"According to the labeling, Addyi is only for premenopausal women, and greatly restricts the use of alcohol, not just prior to a sexual encounter, but all the time, since the drug must be taken every day," he told BioPharma Dive in an interview.
"Setting aside the premenopausal caveat for a moment—which is significant—there will be only two realistic choices for women who take this drug responsibly: reduce alcohol consumption, or reduce use of Addyi. Not to offend or be facetious, but I have to wonder if, in a non-clinical, real-world setting, Addyi without alcohol works better than alcohol without Addyi. And we already know that the off-label use of Addyi with alcohol is potentially deadly, so that’s not an option. In terms of it being well positioned, then, I would say the answer is complex, with many more questions than can be addressed here."
Why Addyi is not Viagra
Calling Addyi the "Pink Viagra" is misleading and medically incorrect. According to Dr. Barry Mennen, a practicing physician in Washington, D.C. with 30 years of pharmaceutical industry experience, "Addyi and Viagra address fundamentally different issues. Viagra deals with function—the inability of a man to achieve and hold an erection for successful intercourse, while Addyi deals with the more subjective and complex issue of sexual desire.
"When the clinical trials were done for the PDE5 inhibitors they measured turgidity, length of time erect, ability to penetrate and other easily quantifiable end points. With Addyi, the only objective measurement was the number of satisfying sexual encounters. Measuring desire is obviously more difficult," he said.
"We have been treating post-menopausal women with dysfunctional sexual issues such as vaginal dryness for years with HRT and/or intravaginal agents. So it seems that treating vaginal dryness in women is much more analogous to treating erectile dysfunction in men. Before Addyi, testosterone was the only modality available for treating hyposexual desire in women and because of the masculinizing side effects, it was used by few physicians."
Let’s talk about sex
Beyond safety concerns, one reason Addyi was rejected previously by the FDA was because of concerns about "marginal effectiveness." But some think that the real challenge is understanding how to gauge sexual satisfaction in women.
"Female sexual desire is complicated," said Judith E. Steinhart, a clinical sexologist and sex educator in New York City. "It is clearly not only physical. It is social and emotional."
In fact, clinical trials were designed to reflect the biopsychosocial reality of how women experience sexuality. In three 24-week, randomized, double-blind, placebo-controlled trials involving 2,400 premenopausal women, women were asked the following questions: "Did you have a sexual event?" and "Was it satisfying to you?" It should be noted that the term "sexual event" is defined as intercourse, masturbation, or any other type of sexual interaction or activity.
It should also be noted that the clinical trials for Addyi only included heterosexual women in relationships with men, and these women had previously had fulfilling sex lives. It would seem that broadening the pool of studied subjects to include women in same-sex relationships would not only be a truly woman-centric move, but also good for marketing—a way to broaden the message and take this topic out of the dark ages.
A good month for sexual satisfaction
Overall, treatment with Addyi increased the number of sexually satisfying experiences (SSEs) by 0.5 to 1 additional events per month compared with placebo. At baseline, the women in the study were experiencing 2.7 to 3 SSEs per month, and by the end of the 24-week period, women treated with Addyi were experiencing 4.4 to 5 SSEs per month. In short, roughly 10% more Addyi-treated women than women treated with placebo reported meaningful improvements in SSEs, sexual desire, or sexual distress.
While these results reflect subjective improvements for Addyi-treated women, Steinhart suggests that the real issues are hard to address pharmacologically. "There are many reasons why women’s desire wanes," she explained. "I keep thinking that in a heterosexual relationship, the most seductive thing a man can say is ‘Honey, I’ll clean the kitchen tonight.’ Sometimes the prescription needs to be more time alone to relax and more time to allow one’s sexual feelings to surface while getting rid of resentments."
Addyi could open the doors to better MD-patient communication
Anecdotally, women who were involved in the Addyi clinical trials have spoken about an increased sense of sexual desire that occurs spontanteously, a "tingling" and a sense of having their former sexual selves restored. There is a subtlety to the response to Addyi, but a response nonetheless. In Treato’s survey, once women found out that an option for low sex drive might become available, 73% of respondents said that they were likely to discuss low sex drive with their physicians.
Dr. Mennen said that he would be willing to prescribe Addyi if he receives inquiries. "One way I believe that Addyi is similar to Viagra is that it will begin to start a dialogue going about this issue," he said.
"The marketing communications that Sprout/Valeant will now put behind this agent will help patients to self-identify, and will undoubtedly lead to higher qualities of life for women who are helped by this drug. Viagra, Levitra, and Cialis certainly did that for millions of men. Will a similar phenomenon happen with Addyi? Only time will tell, but women go to the doctor much more often than men, and the natural place for this discussion to occur would be in the OB-GYN's office. At this point, I do not see internists or family practitioners prescribing Addyi until it has been out for a year or so."
The challenge for marketers
While Treato’s survey results reflect a widespread willingness among women to try Addyi, there are numerous barriers and risks involved. However, even with all of the existing restrictions, Malter foresees rapid uptake.
"While Sprout Pharmaceuticals has committed to delaying consumer marketing for 18 months post-approval, it will be interesting to see how Valeant handles it, unless it was part of the approval agreement and is mandatory," he said.
"The fact that physicians have to 'pass a test' before prescribing Addyi will be nothing more than a speed bump in the process, nor do I think the Boxed Warning will be a huge impediment to prescribing. The demand will be too great.
"Just take a look at Viagra sales, and realize that it’s improbable there are enough men in this country with true ED to support the volume."
One of the main marketing challenges will be reframing the way sexual health is measured—focusing not only on objective, easily quantified outcome metrics, but also more nuanced, flexible assessments of sexual satisfaction. But is this a breakthrough on par with the introduction of oral contraceptives (OCs) or postmenopausal HRT?
"At this point, 'breakthrough' seems a bit strong," said Dr. Mennen. "The market will decide whether it is or not. But even if it is not the equal of HRT or OCs, if it helps tens of thousands of women with hyposexual disorder lead more sexually fulfilling lives, it will be a significant advance."
(Photo: Mock ad created by Treato.)