FDA NewsPerspective

FDA committee recommends ADDYI approval to treat hypoactive sexual desire disorder in pre-menopause

In an 18-to-6 vote at the FDA joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee, and the Drug Safety and Risk Management Advisory Committee, flibanserin was recommended for approval to treat hypoactive sexual desire disorder in premenopausal women.

The non-hormonal drug flibanserin (ADDYI, Sprout Pharmaceuticals), studied for efficacy in more than 11,000 women, gained the recommendation for approval with the requirement that certain risk management options beyond labeling be implemented, according to a news release.

“Yesterday’s vote is going to have a huge impact on the entire future of this field,” Sheryl Kingsberg, PhD, a clinical psychologist and chief of behavioral medicine at University Hospitals Case Medical Center, Cleveland, told Healio.com. “Their vote really was a message to anybody doing any research in this field as to whether or not they could move forward.”

Sheryl Kingsberg

Kingsberg, an investigator in flibanserin trials involving both premenopausal and postmenopausal women, delivered what she called “a necessary informational opening” at the meeting on behalf of Sprout that conveyed the unmet medical need in approximately 16 million women with hypoactive sexual desire disorder (HSDD).

“The advisory committee had very diverse background, therefore it was important that they developed a common understanding of the profound impact of this condition on women and what women actually want from a treatment,” Kingsberg said.

HSDD is the most commonly reported form of female sexual dysfunction and characterized by deficiency or absence of desire for sexual activity, which causes marked distress.

Testimony from patients in the open forum made an impact on the joint committee, according to Kingsberg. “They learned that modest benefit, which is what they perceived from the clinical trials, was actually very meaningful to these patients.”

Three 6-month, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials involving premenopausal women (mean age = 36 years) have shown flibanserin offers statistical improvements on three key endpoints: sexual desire, distress from the loss of sexual desire; and increase in the frequency of satisfying sex.

“In these kinds of trials looking at sexual desire, the endpoints may not show a huge number change, but that’s not what women are looking for,” Kingsberg said. “They’re looking for some restoration of their desire.”

Kingsberg underscored that trial results that appear to demonstrate, as one advisory committee called, “minimal” change actually represent “meaningful” change for women.

“With the idea of satisfying sexual events as a primary endpoint, those who are not in the field might think it’s not a huge number of events that increase,” Kingsberg said. “But women don’t really think about desire in terms of activity as much as they think about it in terms of wanting or the motivation to engage in intimacy with their partner.”

The safety of flibanserin has also been proven in trial data from over 8,500 women, with over 1,000 of those women exposed to treatment for at least 1 year, according to the release. The majority of side effects were mild, with dizziness, nausea and sleepiness reported most commonly.

Although the FDA is not required to accept the recommendation given by the committee, the agency considers it as part of the new drug application review. If approved, flibanserin would be the first authorized to treat HSDD.

“It has been such a long road,” Kingsberg said. Research on flibanserin as a treatment for HSDD has been underway for about 10 years, with phase 3 trials over the last 5.

Flibanserin has an anticipated Prescription Drug User Fee Act date of August 18, according to a Sprout representative.

“We are certainly hopeful the FDA will take the committee’s advice and approve in August,” she said. “If you meet all those endpoints and have good efficacy and risk-benefit profile, and you still don’t get approved, that really sends a message that nothing will get approved.” – by Allegra Tiver

Disclosure: Kingsberg reports being a consultant for Apricus, Emotional Brain, Metagenics, Novo Nordisk, Palatin, Pfizer, Shionogi, Sprout, SST, Teva, TherapeuticsMD and Trimel.



In an 18-to-6 vote at the FDA joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee, and the Drug Safety and Risk Management Advisory Committee, flibanserin was recommended for approval to treat hypoactive sexual desire disorder in premenopausal women.

The non-hormonal drug flibanserin (ADDYI, Sprout Pharmaceuticals), studied for efficacy in more than 11,000 women, gained the recommendation for approval with the requirement that certain risk management options beyond labeling be implemented, according to a news release.

“Yesterday’s vote is going to have a huge impact on the entire future of this field,” Sheryl Kingsberg, PhD, a clinical psychologist and chief of behavioral medicine at University Hospitals Case Medical Center, Cleveland, told Healio.com. “Their vote really was a message to anybody doing any research in this field as to whether or not they could move forward.”

Sheryl Kingsberg

Kingsberg, an investigator in flibanserin trials involving both premenopausal and postmenopausal women, delivered what she called “a necessary informational opening” at the meeting on behalf of Sprout that conveyed the unmet medical need in approximately 16 million women with hypoactive sexual desire disorder (HSDD).

“The advisory committee had very diverse background, therefore it was important that they developed a common understanding of the profound impact of this condition on women and what women actually want from a treatment,” Kingsberg said.

HSDD is the most commonly reported form of female sexual dysfunction and characterized by deficiency or absence of desire for sexual activity, which causes marked distress.

Testimony from patients in the open forum made an impact on the joint committee, according to Kingsberg. “They learned that modest benefit, which is what they perceived from the clinical trials, was actually very meaningful to these patients.”

Three 6-month, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials involving premenopausal women (mean age = 36 years) have shown flibanserin offers statistical improvements on three key endpoints: sexual desire, distress from the loss of sexual desire; and increase in the frequency of satisfying sex.

“In these kinds of trials looking at sexual desire, the endpoints may not show a huge number change, but that’s not what women are looking for,” Kingsberg said. “They’re looking for some restoration of their desire.”

Kingsberg underscored that trial results that appear to demonstrate, as one advisory committee called, “minimal” change actually represent “meaningful” change for women.

“With the idea of satisfying sexual events as a primary endpoint, those who are not in the field might think it’s not a huge number of events that increase,” Kingsberg said. “But women don’t really think about desire in terms of activity as much as they think about it in terms of wanting or the motivation to engage in intimacy with their partner.”

The safety of flibanserin has also been proven in trial data from over 8,500 women, with over 1,000 of those women exposed to treatment for at least 1 year, according to the release. The majority of side effects were mild, with dizziness, nausea and sleepiness reported most commonly.

Although the FDA is not required to accept the recommendation given by the committee, the agency considers it as part of the new drug application review. If approved, flibanserin would be the first authorized to treat HSDD.

“It has been such a long road,” Kingsberg said. Research on flibanserin as a treatment for HSDD has been underway for about 10 years, with phase 3 trials over the last 5.

Flibanserin has an anticipated Prescription Drug User Fee Act date of August 18, according to a Sprout representative.

“We are certainly hopeful the FDA will take the committee’s advice and approve in August,” she said. “If you meet all those endpoints and have good efficacy and risk-benefit profile, and you still don’t get approved, that really sends a message that nothing will get approved.” – by Allegra Tiver

Disclosure: Kingsberg reports being a consultant for Apricus, Emotional Brain, Metagenics, Novo Nordisk, Palatin, Pfizer, Shionogi, Sprout, SST, Teva, TherapeuticsMD and Trimel.



    Perspective
    Irwin Goldstein

    Irwin Goldstein

    June 4, 2015 — by a vote of 18-to-6 — has become a very historic day for women’s health rights. Now, for the first time in history, women have the right to choice in the health concern of distressing low sexual interest or hypoactive sexual desire disorder. 

    There are millions of women who suffer poor life quality, have low self-esteem, and perform uncomfortable “duty sex” because they have an acquired lack to want to have sexual activity. Many of these women do not initiate sexual activity and have no responsiveness to sexual activity once sexual activity begins, but they are motivated to have sexual activity, in part, to maintain and preserve their partner relationship. 

    What has occurred will allow some of them to choose beyond psychologic management into treatment for biologic-based HSDD. Basic science research has shown that some woman with HSDD have inappropriate brain blood flow to sexual reflex centers of the brain. Flibanserin, by increasing excitatory neurotransmitter (norepinephrine and dopamine) and decreasing inhibitory neurotransmitter (serotonin), has been demonstrated to safely and efficaciously help a subgroup of women with HSDD. 

    The availability of an FDA-approved non-hormonal treatment for a female sexual desire disorder will spur on new basic science and clinical research into women’s sexual health and will open the likelihood that female sexual health will be now taught, for the first time, in medical schools and in health care provider residency training programs. 

    Women with asexual health problems will now be able to start a conversation, often for the first time, with their health care providers. July 4, 2015 was a huge and very important day for women’s health.

    • Irwin Goldstein, MD
    • Director, Sexual Medicine, Alvarado Hospital, San Diego, California

    Disclosures: Goldstein reports consultant/advisory board roles at Apricus Biosciences, Emotional Brain, Exploramed, Neogyn, Sprout and Strategic Science & Technologies; speaking for Ascend and Shionogi; and conducting research for Apricus Biosciences, Emotional Brain, Palatin, and TherapeuticsMD.

    Perspective
    Susan Davis

    Susan Davis

    The views about the treatment of female loss of desire, and this medication specifically, are somewhat polarized. However, the FDA has clearly examined the evidence and decided that there is a benefit and there are some potential adverse effects that can be managed. I doubt very much that there will be a stampede for treatment with flibanserin as not all women with low desire will take medication for this, even though it bothers them.

    The “effect size” may appear small, but this is because, like all treatments, there are responders and non-responders. The responders overall do very well with the treatment. Women who try flibanserin will work out very quickly whether it does or does not help them and, as we have seen in studies of testosterone, it is the responders who want to continue with treatment.

    In essence, women will now have a viable option to try, and they will decide if the degree of benefit they experience justifies their continuing treatment. 

    • Susan Davis, MBBS, PhD
    • Endocrinologist, Chair of Women’s Health Monash University School of Public Health and Preventive Medicine, Melbourne, Australia

    Disclosures: Davis reports being a consultant and investigator for Trimel Pharm Canada, receiving research support from Lawley Pharmaceuticals, and speaking for Abbott Australia.