Hormone-free Male birth control clears another regulatory hurdle

Good news! Though, this new medication seems to be slowly acting. It may take weeks to inhibit sperm production.

Turns out, I blogged here already about this same drug, i.e. YourChoice Therapeutics YCT-529, in November of 2022. 😊

"Male birth control that is hormone-free is slated to enter clinical trials after research published in Nature Communications found that the new drug, YCT-529, effectively lowered sperm count in male mice, and was 99% effective in preventing pregnancies."

"... While the FDA has approved over 20 different categories of contraceptives, only two are available for men to prevent pregnancy in their partners — condoms and vasectomies. 25% of women who use contraception use an oral birth control pill, but there are no equivalent methods currently available for men.  ..."

From the abstract:

"Background

The retinoic acid receptor alpha (Rarα) has been validated as a male contraceptive target by genetic knockouts resulting in male sterility. The effects on spermatogenesis in the absence of RARα resemble the loss of RAR signaling in vitamin A deficiency, and the mice are otherwise normal. The effects on spermatogenesis in animals treated orally with the dual RARα/RARγ antagonist BMS-189453 closely phenocopies the absence of RARα function. Notably, the resulting male sterility is reversible. We, therefore, wished to identify RARα−selective inhibitors for potential male non-hormonal contraception.

Methods

YCT-529 was investigated for RARα selective inhibition, physicochemical characteristics, oral bioavailability, and pharmacokinetic properties in mice and non-human primates. It was assessed in mouse mating trials to determine the most effective dosing regimen to induce infertility in male mice and in male non-human primates to reduce sperm levels.

Results

Characterization of YCT-529 shows suitable biochemical, physicochemical, and pharmacokinetic properties for in vivo testing. 

YCT-529 inhibits mouse fertility of male mice within 4 weeks of oral administration, correlating with disrupted spermatogenesis demonstrating specific inhibition of the RARα pathway.

Within 6 weeks after cessation of dosing, mouse fertility reverses.

Furthermore, YCT-529 inhibits sperm production in a non-human primate model within 2 weeks of oral dosing without adverse side effects. Within 10–15 weeks after cessation of dosing, non-human primates’ sperm counts fully reverses.

Conclusions

These results lay the groundwork for evaluating YCT-529 in human clinical trials."

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First hormone-free male birth control pill clears another milestone (original news release)

Targeting the retinoid signaling pathway with YCT-529 for effective and reversible oral contraception in mice and primates (open access)

Fig. 6: Decrease and recovery of sperm counts and unchanged hormone levels in cynomolgus monkeys.