Addyi is intended to increase libido in pre-menopausal women
The drug, which will have a label indication for hypoactive sexual desire disorder (HDSS), was twice rejected by the agency in earlier attempts.
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"Today's approval provides women distressed by their low sexual desire with an approved treatment option," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research (CDER) in a press release.
"The FDA strives to protect and advance the health of women, and we are
committed to supporting the development of safe and effective
treatments for female sexual dysfunction.""Because of a potentially serious interaction with alcohol, treatment with Addyi will only be available through certified health care professionals and certified pharmacies," Woodock added. The FDA ordered a Risk Evaluation and Mitigation Strategies (REMS) program that mandates special training for prescribers.
The label will include a boxed warning to underscore the risks of severe hypotension and syncope among patients who drink alcohol while taking the drug and for women who use "moderate or strong CYP3A4 inhibitors" and those with liver impairments. Addyi is contraindicated for all such patients.
Cindy Whitehead, CEO of Sprout Pharmaceuticals of Raleigh, N.C., the drug's manufacturer, told MedPage Today, "I think that it's just an unbelievable breakthrough moment to finally remove some of the stigma that has mired the progress for this condition and offer potential hope for these women."
Not surprisingly Sheryl Kingsberg, PhD, a reproductive biology and psychiatry professor at Case Western Reserve University School of Medicine who consults for Sprout, called the FDA's decision the biggest advancement in sexual health since the pill.
Sprout describes HSDD on its website as "a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty." The sponsor stresses that the diagnosis is not associated with "a medical, substance-related, psychiatric (e.g., depression), or other sexual condition."
The drug has frequently been dubbed "the female Viagra," although the two drugs have different mechanisms: Viagra increases blood flow to the penis and flibanserin targets receptors in the brain though to enhance libido.
At a meeting of the FDA's Bone Reproductive and Urologic Drugs Advisory Committee in June, the panel voted 18-6 in favor of approving the new treatment with the caveat that "certain risk management options beyond labeling," such as provider certification and postmarketing studies be required.
However, a number of the 18 favorable votes were lukewarm in their endorsement.
Curiously, Jeanmarie Perrone, MD, a professor at the Hospital of the University of Pennsylvania in Philadelphia, recommended approval of flibanserin but "applauded" those panelists who voted against the drug.
"I think we've moved the needle at this committee towards marginal drug acceptance using [Risk Evaluation and Mitigation Strategies] as a tool that shifts the risk-benefit towards accepting these [drugs] and then modifying afterwards." She also said she hoped this approach wouldn't lead to drug withdrawals in the future.
All three trials conducted by the sponsor showed "statistically significant improvement" in the number of satisfying sexual events (SSE) and a reduction of sex-related distress in participants taking flibanserin compared with control participants, according to FDA reviewers. The sponsor drug also showed a median placebo-corrected increase of approximately 0.5-1.0 SSEs per month, from the median baseline of two to three events per month.
Still, the sponsor, Sprout, has been skewered by opponents calling flibanserin a "sham drug" invented to treat an imaginary disease.
Lisa Larkin, MD, associate professor of obstetrics and gynecology at the University of Cincinnati College of Medicine, who spoke during the public hearing in June told the advisory committee, "I take real issue with those who suggest that low libido in women is always the result of relationship or situational issues, anxiety, depression, something that can always be addressed in psychotherapy or that pharma has somehow created this disorder as a niche for a drug."
Whitehead said HSDD has been recognized in the medical literature since 1977. If she was truly responsible for inventing the disease she said, "I would have come up with this idea when I was 5-years old."
Critics have also accused the company of astroturfing, claiming that the Even the Score campaign which champions the drug on the basis of gender equality, is masterful marketing dressed up as a grass roots movement. The organization boasts a petition signed by 11 members of Congress.
As for transparency, the campaign's website does list Sprout on its "about us" below 19 other nonprofits in a category marked "other supporters."
Clinicians weigh in
Cynthia Bednarchik, MS, FN-PBC, an advanced practice nurse at the Southern Illinois School of Medicine said she feels too much attention has been given to the side effects of the drug, which include dizziness, fatigue and nausea. "These are some of the same side effects that all central nervous system medications carry. It's no different than an over-the-counter Benadryl." While the side effects of Viagra and Cialis include visual disturbances and cardiovascular issues.
"I think women are smart enough to know what drugs they want to put in their body and what drugs they don't want to put in their body," she said.
Danielle Staecker, MD, FACOG, a professor at the Center for Pelvic Pain and Sexual Wellness at Kansas University Medical Center in Kansas City was more hesitant. Staecker told MedPage Today in an email, "I think Flibanserin has significant side effects with only modest improvement in libido." Staecker said she worried that some clinicians would prescribe flibanserin without considering the many factors involved in libido," including medical co-morbidities and chronic pain conditions."
Philip Hanno, MD, medical director for the Department of Clinical Effectiveness and Quality Improvement at the University of Pennsylvania Health System and a member of the advisory committee who voted against recommending flibanserin approval told MedPage Today, he would not prescribe the drug. "I think the efficacy is marginal and the side effects are potentially significant," he said.
Those who compare flibanserin to Viagra ignore key differences in how the drugs are used.
Viagra is taken on-demand while flibanserin is prescribed for daily use and "[t]here's almost never been another drug with the efficacy of Viagra," Hanno said, but flibanserin "barely beat placebo."
As for safety, sildenafil (Viagra) has been used by millions of men. If flibanserin is expanded to the same number of women, particularly young women who may be having children, Hanno said the safety profile may change.
Flibanserin could turn out to be perfectly safe, he said but "once a drug gets approved, it's very hard to get it unapproved."
Lauren Streicher, MD, professor of Obstetrics and Gynecology at the Feinberg School of Medicine at Northwestern University, in Chicago, said its important to look more closely at the critique of the drug as having only a "modest" improvement. She compares treating someone with HSDD to treating a depressed patient.
"Your goal is not to make them euphoric. You don't want them dancing through the streets giggling. You want them to feel normal," she said. And so a "modest" increase in this case is what's needed."
Melissa Goist, MD, a professor at the Ohio State University Wexner Medical Center, in Columbus, Ohio, and a physician specializing in obstetrics and gynecology said the drug's impact might not be as broad as the publicity seems to suggest.
"It's not going to be a miracle medication for all women," she said, but that it might help 10-15% of women. While she said she would prescribe the drug to the "right patients," she also stressed looking at the many components involved in libido.
"Sometimes there are things in people's lives that you can alter and change before having to give them a medication. It's just a matter of getting to the root of the problem."
The politics of the matter
John Thorp Jr., MD, professor of obstetrics and gynecology at the University of North Carolina School of Medicine said the sponsor tried a new approach in order to gain approval in creating "a successful popular movement to make the very specific argument that 'you approved so called lifestyle drugs for men in terms of erectile dysfunction, why wouldn't you do the same thing for women?'."
"I think that [Sprout] has shown that the FDA can be influenced politically, at least along the lines of gender inequality," said Thorp said who added that other drug companies will be sure to employ this tactic going forward.
Despite his concerns, Thorp said he would prescribe the drug to patients "for whom this [condition] is a big enough issue." But Thorp was not a disinterested party since he was one of the North American researchers investigating flibanserin for a previous sponsor, Boehringer Ingelheim, which later abandoned the drug's development.)
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