麻豆传媒

BOSTON -- Most men using a daily transdermal hormone gel had quick suppression of sperm count down to contraceptive levels, according to results from a phase IIb clinical trial.

With daily skin application of the Nes/T gel -- a combination of segesterone acetate (Nestorone) and testosterone (8 mg/74 mg per 5 mL) -- 86% of men achieved 1 million/mL or less of sperm by week 15, reported Diana Blithe, PhD, chief of the Contraceptive Development Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A fifth of men reached this sperm suppression level by week 5, 52% reached it by week 8 (the median time to suppression), and 64% reached it by week 9, she explained at ENDO 2024, the annual meeting of the Endocrine Society.

This level of sperm suppression occurred more quickly compared with prior studies of investigational male birth control options, which reported median suppression times of around 12 to 15 weeks. "That's exciting because it will make this product more attractive and we may even be able to show a faster suppression if we have more timepoints at the earlier portion [of the trial]," Blithe noted.

"We weren't expecting this, so we didn't measure at 4, 5, 6 weeks on everybody and we don't know how many of them actually might have been suppressed prior to 8 weeks," she added.

Roughly one out of 10 million sperm enter the fallopian tube to fertilize an egg, and while it only takes one, Blithe said that a sperm concentration under 1 million/mL is considered effective for contraception.

The gel utilizes a similar hormonal approach seen in female birth control, as segesterone acetate is the same ingredient of the Annovera vaginal birth control ring, but Blithe pointed out that testosterone replacement is a key component to this compound.

"If we add a progestin similar to what we use in the female [birth control], we block [luteinizing hormone, follicle stimulating hormone, and gonadotropin-releasing hormone] and stop the production of testosterone in the testis and that stops spermatogenesis," she explained. "However, it also lowers the serum testosterone below a certain level and that would stop additional functions that are dependent on androgens, such as sexual function."

She highlighted the importance of replacing the testosterone level: "It's sort of a Goldilocks -- not too high, not too low -- just the right amount of testosterone for maintaining everything in the blood."

Right now, men only have two options for contraceptive methods: vasectomy, which is highly effective but not easily reversible, and condoms, which are less effective. "Men need and want more options, such as an effective, reversible male method," said Blithe.

For this study, couples were recruited from the U.S., South America, Europe, and Africa, and 222 healthy men self-administered the gel daily to the shoulders, similar to transdermal testosterone replacement therapy. Only men with sperm counts over 15 million/mL at baseline were included.

The trial period spanned about 2 years. The initial screening and suppression phase took place up to week 24, followed by a 52-week efficacy phase, and ended with an 8- to 24-week recovery phase during which sperm counts rebounded to normal. Sperm counts were obtained every 4 weeks, and two consecutive sperm counts under 1 million/mL were required to enter the efficacy phase. At this point, couples stopped using any other contraceptive method.

The gel received positive comments from the couples in the trial, with men saying it was easy to use and something they've always wanted, that it became part of their routine, and that they wished they could continue using the product. Female partners also had positive things to say about the experience, saying they wished they didn't have to go back to their old contraceptive method.

"This is actually a women's health issue, in addition to being a male health issue," said Blithe.

While there are other male birth control methods in the pipeline, the Nes/T gel is currently the furthest along in development.

The next step is to meet with the FDA and initiate a phase III study, Blithe noted. The FDA "haven't had to provide guidelines for approval for a male method because nothing has reached this stage, so they haven't provided it yet. The study is still ongoing. We hope to finish by the end of the year and present the data to the FDA and then get their guidance on the path to approval."

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