Sildenafil Cream Passed Its First Big Safety Trial

There is a version of sildenafil, the active ingredient in Viagra, that you rub on instead of swallowing. Daré Bioscience announced on Thursday, October 8 that clinical data from a phase one study of its topical sildenafil cream would be presented at the Sexual Medicine Society of North America annual fall meeting in Orlando, Florida, held October 8 through 11. The company is developing the sildenafil cream as a treatment for female sexual arousal disorder, a condition that currently has no FDA approved therapy.

The presentation, delivered Friday by the company's medical director, Dr. Annie Thurman, covered an open label, single dose, randomized trial that compared the sildenafil cream against oral sildenafil in healthy adult men, measuring adverse events and relative bioavailability. The finding the company highlighted, in its announcement, was that the sildenafil cream can deliver the drug locally with substantially lower systemic exposure than the pill. For a drug whose oral form is known for body-wide side effects like headache, flushing, nausea, and dizziness, that lower exposure is the entire reason the cream exists.

What the earlier women's trial showed

The strongest evidence for the cream so far comes from the phase two RESPOND trial, which enrolled two hundred premenopausal women with female sexual arousal disorder and randomly assigned them to sildenafil cream or a placebo cream. The main measures were changes from baseline to week twelve in an arousal sensation score and a sexual distress scale. Efficacy results were published in Obstetrics and Gynecology, the journal of the American College of Obstetricians and Gynecologists, with safety data in the Journal of Sexual Medicine.

On the full trial population, the cream did not beat placebo on every endpoint. But in an exploratory subset, women with the disorder with or without decreased desire, the sildenafil cream produced significantly higher arousal sensation scores, improved desire and orgasm scores, and less sexual distress than placebo, according to a Daré announcement on the publication.

"The data from the phase two RESPOND study demonstrate that sildenafil cream treatment reduced sexual distress across multiple measures in a clinically meaningful way," said Dr. Andrew Goldstein, a medical advisor for Daré Bioscience and former president of the International Society for the Study of Women's Sexual Health, in the release. He also reported that sildenafil cream users had more sexual experiences overall, and more solo experiences, which accounted for about one in five of the recorded sexual events.

The safety profile looked manageable. Seventy-eight treatment emergent adverse events were reported among twenty-nine of ninety-nine women using the sildenafil cream, compared with sixty-five events among twenty-eight of ninety-four women using the placebo cream, a difference the researchers said was not statistically significant. Every event was mild or moderate, and the most common treatment related complaint was discomfort where the cream was applied, which led four cream users and two placebo users to stop treatment. Partners exposed to the cream reported a similarly low rate of mild events.

Dr. Thurman tied those safety results to the cream's low systemic exposure. "Because oral sildenafil has known hypotensive effects, we were watching for related side effects such as headache, flushing, nausea, and dizziness," she said in a news release on the findings. "In the RESPOND study with our topical application, however, we did not see these effects, likely due to the hundred-fold lower systemic exposure as compared to oral dosing."

Why a cream for women's arousal matters

Female sexual arousal disorder is common and has no approved drug treatment, which is why Daré is positioning its sildenafil cream as a potential first-in-category therapy. The San Diego company describes itself as solely focused on closing the gap between promising science and real world solutions in women's health, and its chief executive, Sabrina Martucci Johnson, has said the company will keep working with the FDA to finalize a planned phase three program for the cream.

That framing carries weight because women's sexual health has historically drawn a fraction of the research money and attention that men's sexual health receives. For context, the FDA only recently began formally reviewing whether testosterone therapy has a place in women's care at all, holding its first workshop on the question this year, which GenZ NewZ covered in September. A topical treatment that targets arousal directly, without the body-wide effects of a pill, would fill a real hole in the options available to women.

What happens next

Daré has already begun putting the sildenafil cream in women's hands outside of clinical trials. A Urology Times report late last year said the cream, marketed under the name DARE to PLAY, was available to prescribe in select states, with availability expanding through December and into early this year. "As more women speak openly about their sexual health, the need for research-backed solutions has never been greater," said Dr. Irwin Goldstein, director of San Diego Sexual Medicine, in the company's release.

The sexual wellness beat has been busy lately. Researchers are also testing a twice yearly HIV prevention shot and studying how a traditional herb affects desire. But a topical sildenafil cream sits in its own lane. It repurposes one of the best understood drugs in sexual medicine for a population that has never had an approved option. The coming phase three program will determine whether the early signals hold up, and whether women's sexual medicine finally gets its first approved arousal treatment.