'Female Viagra' Foes Denounce PR Campaign to Win FDA Approval

August 10, 2015

Some 200 researchers, clinicians, and sex therapists are urging the US Food and Drug Administration (FDA) to withhold its approval of flibanserin (Addyi, Sprout Pharmaceuticals), or the "female Viagra," in the face of what they say is an unprecedented "manufacturer-funded public relations campaign that accused the FDA of sexism."

The campaign, called Even the Score, claims that the lack of a single FDA-approved drug for sexual dysfunction in women compared with 26 for the same problem in men (17 of them are different formulations of testosterone) demonstrates a "persistent gender inequity" at the FDA. Supporters of Even the Score include not only the drug's manufacturer, but also the National Organization for Women, the Association of Reproductive Health Professionals, the American College of Nurse-Midwives, and the National Hispanic Medical Association.

Opponents of the libido-boosting drug contend that the appeal to gender justice is just a smoke screen for a medication of marginal benefit and great potential for misuse if it is prescribed off-label, as many expect it will be. For one thing, any approval of the once-a-day drug will come with some kind of warning about the increased risk for somnolence, hypotension, and syncope when patients use alcohol at the same time.

"As sexologists, we can say with confidence that this advice is both preposterous and doomed," wrote Leonore Tiefer, PhD, a clinical associate professor of psychiatry at the New York University School of Medicine and the lead signatory of one of two letters that the FDA recently received from flibanserin opponents.

Her concerns were echoed by several members of the FDA advisory committee that recommended approval of flibanserin in June for hypoactive sexual desire disorder (HSDD) in premenopausal women. Writing in the Journal of the American Medical Association last month, three committee members called the Even the Score campaign and the claims of gender bias at the FDA "particularly noteworthy." The authors, two of whom recommended approval, said the FDA would have to make the final decision in a "politically charged atmosphere."

A psychiatrist who has worked as a consultant to Sprout Pharmaceuticals and other drug companies defends Even the Score as a good-faith effort at advocacy and education. And it isn't a corporate front group, she said.

"I think most people would be hard pressed to say that a group like the National Consumer League [a flibanserin supporter] is being manipulated by a pharmaceutical company," said Anita Clayton, MD, interim chair of psychiatry and neurobehavioral sciences at the University of Virginia, in an interview with Medscape Medical News.

An FDA decision on flibanserin is expected by August 18.

Otherwise Happily Married, but Low on Libido

Flibanserin was originally developed as an antidepressant. The FDA has twice turned it down as a libido booster, once in 2010 when it belonged to Boehringer Ingelheim and again in 2013, after Sprout had acquired it. At the same time, the agency characterizes HSDD as an "unmet medical need." Two studies put the prevalence of HSDD at 8% to 14% of premenopausal women, according to the agency.

The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-4), states that the condition is marked by "persistently or recurrently deficient (or absent) sexual fantasies and desire for sex," and distress and interpersonal conflicts caused by this disturbance. It does not stem from a general medical condition, the adverse effects of a drug, or an anxiety or mood disorder.

Dr Clayton described a typical patient with HSDD as an otherwise happily married woman who has a baby and then loses her desire for sex. "They're coming in with this three years after the baby," Dr Clayton said. "They're still in love with their partner. They don't have any significant conflicts. They view [HSDD] as a real loss."

Flibanserin cleared the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee in an 18-to-6 vote. The advisory group determined that the drug was effective based on a phase 3 clinical trial designed with FDA input. It showed that women on the drug scored 0.3 to 0.4 higher on a scale of 1.2 to 6 answering questions from the Female Sexual Function Index about desire. They also reported an increase of 0.5 to 1 satisfying sexual events per month and an improvement of 0.3 to 0.4 on the four-point Female Sexual Distress Scale. All of these results, corrected for a placebo effect, were deemed statistically significant.

In addition, almost 52% of women receiving the drug said they experienced some measure of libido improvement. However, 38% of women on a placebo said the same thing, causing committee members to question how beneficial the drug really was.

The 18 committee members who recommended flibanserin for approval did so on the condition of a Risk Evaluation and Mitigation Strategy to ensure that prescribers are educated about the drug's risks, which include the aforementioned somnolence, dizziness, syncope, and hypotension. Alcohol, oral contraceptives, and other drugs can amplify these effects. Night-time dosing recommended by Sprout would minimize somnolence, which doesn't persist into the next day.

The manufacturer's proposed label for the drug states that "patients should be advised to avoid alcohol until they know how flibanserin affects them."

One of the letters that the FDA recently received from flibanserin opponents focused on its safety. It predicted "an epidemic of serious adverse events" when the drug gets prescribed to women with heart problems or other comorbid conditions, those on multiple drugs, and social drinkers.

"The harms and narrow margin of safety of flibanserin may be acceptable in a cancer drug, but are entirely unacceptable in a drug given to healthy women for a questionable condition," the letter said. It also said that expecting patients who enjoy alcohol to become teetotalers would be "unreasonable."

The 103 signatories to the letter includes Sidney Wolfe, MD, senior advisor at Public Citizen's Health Research Group, Sari van Anders, PhD, editor of the Annual Review of Sex Research, and other researchers and clinicians from all over the world. The lead signatory is Adriane Fugh-Berman, MD, director of PharmedOut, a project at Georgetown University Medical Center, Washington, DC, to educate physicians about inappropriate pharmaceutical marketing practices.

Supporters of flibanserin say that sildenafil and other FDA-approved drugs for men with erectile dysfunction pose the same degree of risk — if not more — as flibanserin. And yet men get to decide whether they want to take that risk, the argument goes.

Dr Clayton, who served as a clinical trial investigator for flibanserin, told Medscape Medical News that alcohol use isn't as problematic as critics say. Syncope rates for women taking flibanserin in the phase 3 clinical trials — 60% of whom were social or moderate drinkers — were the same as those for women receiving a placebo, she said (0.3% for the placebo versus 0.4% for any dose of flibanserin). The only alarm bells about alcohol use came from a separate study designed to mimic binge drinking in 23 men and 2 women, all of whom were moderate drinkers. Dr Clayton said it was difficult to find female subjects for the test.

If women drink in moderation and know that combining alcohol and flibanserin might have side effects, they "can make choices and use this drug appropriately," said Dr Clayton, who was offered by Sprout's public relations firm when Medscape Medical News requested an interview with the company. "If you're a heavy drinker, and I know that as your provider, then perhaps I wouldn't recommend this drug to you, or I'd recommend that you need to cut back on your alcohol, and then let's see."

Desire and Its Origins

The other antiflibanserin letter that the FDA received last month came from Dr Tiefer and 133 other psychiatrists, psychologists, sex therapists, sex educators, and authors of books such as A Tired Woman's Guide to Passionate Sex and Nymphomania: A History. This letter disputes how Sprout characterizes the problem of low female libido and how to treat it.

The letter argues that the diagnosis of HSDD appears in DSM-4, but not in the new DSM-5. There, HSDD is subsumed in the catchall diagnosis of Female Sexual Interest/Arousal Disorder. Dr Tiefer and her allies wrote that the change reflects a shift from viewing female sexual desire as an intrinsic, internal, spontaneous urge toward a different model in which desire interacts with "psychological, stimulus, and relational context."

"Women's ratings of their 'level of desire' fluctuate markedly in conjunction with life events," they wrote. They said that the use of flibanserin could give short shrift to sex education and counseling, as if episodes of low libido were amenable only to medication.

Dr Tiefer told Medscape Medical News that science has moved on from the theory of female sexuality behind the flibanserin application. "It's not regarded as accurate anymore," she said. Desire "just doesn't arise from sitting around."

Dr Clayton counters that HSDD still remains in the ICD-10 diagnostic code set used by clinicians. And while some women who engage in sex may not say they experience desire out of the blue, many women do, she said.

"The Rhetoric Is Winning"

Adding to the scientific controversy surrounding flibanserin is the Even the Score advocacy campaign, which has Facebook and Twitter pages in addition to a website. Visitors to the website can watch a video presentation by Dr Clayton on HSDD, sign a petition to the FDA, and write their congressman. The campaign's Facebook page features images of feminist heroes such as Betty Friedan, Sandra Day O'Connor, and early 20th-century suffragettes.

Even the Score officially launched in June 2014 with the help of a public relations firm in Washington, DC, called Blue Engine Message and Media. Jaime Horn, a communication specialist there, told Medscape Medical News that a group of women's health advocates who included a consultant to Sprout Pharmaceuticals approached her company about creating the campaign.

Lissa Pavluk, an account executive at Edelman, Sprout's public relations firm, confirmed in an interview that the drug company has contributed financially to Even the Score, as have other groups. Horn at Blue Engine Message and Media said that Even the Score "does not disclose individual breakdowns of contributions made by its members."

Medscape Medical News asked to speak to a spokesperson for Even the Score, such as chairperson Susan Scanlan. The spokesperson proffered was Sally Greenberg, executive director of the National Consumers League. Greenberg said that although her group is not an official member of the Even the Score coalition it supports the campaign because it is "a really important voice for awareness about gender parity and the need to address women's sexual dysfunction."

To FDA letter-writer Dr Tiefer, Even the Score is a "fraudulent player" in the deliberations on flibanserin.

"The loudest spokespeople in this have conflicts of interest," she told Medscape Medical News. "They're part professionals and part promoters."

Even the Score drew fire almost as soon as it went public last year. In October 2014, the British Medical Journal published an article titled Evening the Score on Sex Drugs: Feminist Movement or Marketing Masquerade? The author, Australian researcher and journalist Ray Moynihan, PhD, described the campaign as a Sprout-inspired effort to bully the FDA into approving a drug for an exaggerated medical need.

Some women's groups also look askance at Even the Score.

"Even the Score's [flibanserin] petition and attempts to make this a conversation about gender equality is misleading and dangerous," the National Women's Health Network (NWHN) states on its website. "While the FDA should be held accountable for gender equality, it should not compromise the safety of women's health by approving a drug that is not effective and not safe."

In an opinion piece published in the Washington Post in June, NWHN executive director Cindy Pearson described how Even the Score brought dozens of speakers to the FDA advisory committee hearing to testify in favor of flibanserin.

The committee vote recommending approval, wrote Pearson, "suggests that the rhetoric is winning."

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