Intrinsa stalled by concerns about safety

Touted as female Viagra, Procter & Gamble's testosterone patch for women, Intrinsa, was slated as the next blockbuster lifestyle drug. But the U.S. Food and Drug Administration Advisory Committee for Reproductive Health Drugs put the brakes on its fast-track approval in early December 2004.

And since Dec. 21, 2004, Intrinsa's manufacturer has been confirming its intent to withdraw the current FDA application and resubmit a new application to address concerns raised by the advisory panel.

"The 17-0 vote really focused on safety," said Irwin Goldstein, MD, professor of urology and gynecology at Boston University School of Medicine and director of its Institute for Sexual Medicine. "[The manufacturer] needs to document more than six months of data."

Intrinsa would have been the first FDA-approved drug for women with sexual health problems. And despite the call for more safety data, Dr. Goldstein said, this is a new arena. Historically, women's sexual problems have been viewed as being in the brain rather than the body, so the fact that there's a drug in the pipeline designed to address an altered biochemistry is promising.

"The efficacy was favorably viewed by the committee," he said. "When a new class of drugs comes out, it's exciting, and to one day get approval by a government regulating agency for the treatment of women's sexual health ... it has never happened before. Hopefully, this is the beginning."

Worn on the abdomen, Intrinsa releases a small amount of natural testosterone in an attempt to compensate for a drop experienced by some women as they age. The 24-week randomized, double-blind, multicenter trial was limited to surgically menopausal women with hypoactive sexual desire disorder. Participants recorded an increase in satisfying sexual activity versus placebo. Still, the committee focused on the study's limits rather than the drug's efficacy.

"It needs to be studied on all women," said Leah Raye Mabry, MD, a family physician in San Antonio and an officer of the American Academy of Family Physicians. "This was targeted toward a special group of women. And there were concerns that the drug would be used off-label for groups not studied."

But off-label use of hormones to boost a woman's libido is common and has been going on for years. The problem is that there are no studies as to the long-term effects. "There was a concern it would end up like Viagra, and even if doctors were reluctant to prescribe, patients would be almost demanding that doctors give them a chance to try it," Dr. Mabry said.

In opposition to Intrinsa's approval, Leonore Tiefer, PhD, a psychologist at New York University School of Medicine, lauds the FDA committee. "Approval would have been premature. ... My major concern besides safety was the promotional campaign P&G was going to roll out."

Dr. Tiefer said the educational campaign was to swamp the airwaves and health magazines with education materials about Hypoactive Sexual Desire Disorder. "In this country, we lack comprehensive sexual education, and I was horrified that the first education would come from P&G."

In the background

It's been more than two years since findings from the Women's Health Initiative changed the hormone therapy landscape, and the dramatic swing away from its combined use has somewhat tempered of late. But there's still reason for caution when prescribing hormones.

The WHI has shown that data are needed long term, and that's the piece missing from the Intrinsa studies, Dr. Goldstein said. "What about using it for women with angina, when is it contraindicated? Viagra has that; for Viagra, there is a paradigm," he says. "That's clearly what's missing from the knowledge."

In addition to safety concerns, the jury is still out on using hormones to improve sex drive. "There have been too few studies to prove that taking estrogen or the male hormone testosterone -- either orally or topically -- can improve a woman's sexual libido," according to findings published in a special supplement to the October 2004 issue of Obstetrics and Gynecology.

In an early December 2004 response to the advisory panel vote, P&G officials expressed disappointment about the outcome but noted that the committee did recognize that Intrinsa is clinically effective. Then, the decision to submit a new application made news the day the FDA was expected to respond to the previous one. According to P&G spokeswoman Mary Johnson, the next effort will include data from phase III trials involving naturally menopausal women. "This was something the committee members were interested in," she said.

Currently, there is no timeline for when this application will be submitted, she said, adding that P&G hopes to meet with FDA officials sometime this month to determine how to address in a practical way other questions and concerns raised during the advisory panel's meeting.

Meanwhile, experts called for more education about women's sexual health. All this attention to female sexual response is good, Dr. Mabry said. "Women should expect to have a full life emotionally, physically and sexually," she said. "I think bringing forth these concerns as function decreases will help everybody. And it's been proven that people with an active sexual life live longer."

Until recently, research on therapies for female sexual dysfunction lagged. But with the market for female sexual response products projected to reach $3 billion, a growing number of pharmaceutical manufacturers are showing interest. Current trials are investigating pills, patches, creams, gels and sprays. Companies such as Vivus are testing a synthetic blood vessel dilator, prostaglandin E-1, also found in semen; BioSante is in late-stage studies of LibiGel; Nastech Pharmaceutical is in phase II trails for a nasal spray that may work on both mind and body by stimulating dopamine receptors in the hypothalamus.

But it is not only about medicine. "What we took for granted as young people maybe we can't take for granted now because of physiological changes," Dr. Mabry said. "What I hope is that doctors are asking about this in their everyday practice. Doctors need to ask, to listen to the patient, to understand and work with the patient and partner."