A novel male contraceptive gel achieved sperm suppression sooner than expected in an ongoing Phase 2b clinical trial, according to data presented at an oral abstract session at ENDO 2024, the annual meeting of the Endocrine Society in Boston.
The once-daily gel, a combination of the hormones Nestorone (segesterone acetate) and testosterone, is effective, reversible, safe, and was accepted by men and couples enrolled in the 2-year study. The gel, which contains 8 mg of Nestorone and 74 mg of testosterone, is applied daily by men on each shoulder blade. The ongoing, multisite study includes 222 men who used the gel for at least 3 weeks.
Male Contraception Offers a Necessary and Effective Alternative
This is the first user-administered transdermal gel under study for male contraception, which may be a more attractive option than previously researched male hormonal contraceptives that included injectables and implants and required regular visits to a clinic to receive treatments.
“Despite the need for men to apply the gel daily for effectiveness, we show here that the time to reach a sperm threshold we know is compatible with effective male contraception (< 1 million sperm/ml of ejaculate) was no longer, and perhaps shorter, than that observed for clinic-administered methods,” said one of the lead investigators, Stephanie Page, MD, PhD, who is an academic physician and head of the division of metabolism, endocrinology and nutrition at the University of Washington. Dr. Page holds the Robert B. McMillen Professorship in Lipid Research and serves as co-director of the UW Medicine Diabetes Institute.
“This is good news, and perhaps a bit unexpected, since injectable methods provide higher peak hormone levels and by and large eliminate compliance as a confounder,” Dr. Page noted.
During the presentation at ENDO 2024, Danielle Gross, a post-baccalaureate fellow in the Contraceptive Development Program at the NIH who was involved in the study, noted that the only contraceptive options currently available to men are vasectomy and condoms. “Many men actually expressed the desire to use contraception, and they need and want more contraceptive options,” she said.
“Safe, effective, reversible options for male contraception are appealing to men and their partners,” agreed Carolyn Allan MBBS (Hons), PhD, DRCOG (UK), FRACP, adjunct clinical associate professor at the Hudson Centre for Endocrinology and Metabolism, School of Clinical Sciences at Monash Health. Dr. Allan, who is not connected to the study, added that “the lack of side effects and faster time than expected to sperm suppression are encouraging early results.” Dr. Allan is also on the faculty of medicine, nursing, and health sciences at Monash University, and head of Endocrine Services in Pregnancy at Monash Health in Melbourne, Australia.
Surprising Trial Results are Encouraging
The current phase of this study had three parts:
a screening and suppression phase lasting 8 to 24 weeks, in which the sperm count is measured until suppression is achieved
a 1-year treatment phase when the couple uses only the gel as their method of birth control
a recovery phase lasting 8 to 24 weeks, in which the gel is stopped, and the sperm count returns to normal
The research team estimated that the median time to spermatogenic suppression would be approximately 12 weeks based on previous studies of male hormonal contraceptives that found a range of 12 to 15 weeks. In the study, however, the median time to suppression in men using the gel was less than 8 weeks, and by 12 weeks, about 80% had achieved suppression.
This faster timeline of suppression surprised the research team, said senior researcher Diana Blithe, PhD, chief of the Contraceptive Development Program at the National Institutes of Health, in a press conference at ENDO 2024. She added that perhaps earlier assessments during weeks 4 through 6 may have revealed an even faster average time to suppression.
Positive Feedback from Both Male and Female Participants
Participants in the study have given positive feedback about their experiences using the combination gel, according to the researchers. During an ENDO press conference Dr. Blithe shared some comments from men who described it as “easy” and “something I’ve always wanted,” adding that her favorite comment was, “Can I re-enroll in the study?” Given that the study lasts 2 years and includes many visits to the clinic, the fact that men want to continue is “an endorsement for the product that’s stronger than anything I could convey,” she said.
Another one of the study’s co-investigators, Bradley Anawalt, MD, chief of medicine at the University of Washington Medical Center, has also heard positive feedback from participants. “The female participants of the trial have found it to be a good form of contraception,” he told MedCentral. “We’re having couples say that they really would love to have this product on the market so that they could continue to use it.”
Dr. Blithe added that women in the study expressed disappointment that they had to resume their previous methods of birth control as they and their partner approached the end of the treatment phase. Understanding women’s perspectives of the experience is important, she said, because “this is actually a women’s health issue in addition to being a male health issue.”
Plans for the Male Contraception Pipeline
While the research team is working to finish data collection and analysis of the Phase 2b trial, it is also collaborating with the FDA on the design of the Phase 3 study. The gel is the first male contraceptive to have progressed this far in the process, and the FDA will provide guidelines on the next steps.
“Overall, these data suggest that a self-administered male hormonal contraceptive may be a viable addition to the male contraceptive pipeline,” said Dr. Page.