Cornell's On-Demand Male Contraceptive Pill Nears First Trial

Weill Cornell Medicine received a four-year, $8.2 million grant from the National Institute of Child Health and Human Development to develop and test an on-demand male contraceptive pill, according to the Cornell Chronicle. The male contraceptive pill is designed to be taken 30 minutes before sex, and it stops sperm from swimming for six to eight hours before fertility returns to normal, according to the Cornell Chronicle. Professors of pharmacology Jochen Buck and Lonny Levin lead the project, and the grant will pay for the toxicology and safety studies needed before the drug can be tested in people, according to the Cornell Chronicle.

About half of all pregnancies worldwide are unplanned, and men have long had only condoms and vasectomies as contraceptive options, according to the Cornell Chronicle. That gap has left most of the work of contraception to women, who often rely on long-term hormonal contraceptives that may bring sexual side effects, Levin said. A short-acting option for men would spread that responsibility more evenly, and Levin said couples could one day discuss male contraceptives at a pharmacy the way they now discuss other family planning choices.

The male contraceptive pill works by blocking an enzyme called soluble adenylyl cyclase, known as sAC, which sperm need in order to swim, according to the Cornell Chronicle. Proof-of-concept research published in Nature Communications in 2023 showed that blocking sAC rendered sperm immobile and prevented pregnancies in preclinical models, according to the Cornell Chronicle. Peter Meinke, an assistant professor of pharmacology at Weill Cornell, has since helped turn sAC inhibitors into drug candidates suitable for humans, according to the Cornell Chronicle.

The new grant is the third in a series awarded to the shared laboratory run by Buck and Levin, according to the Cornell Chronicle. A first grant from the Contraceptive Development Research Center Program at the same institute funded the proof-of-concept studies in 2020, and a second grant paid for refining and testing different compounds, according to the Cornell Chronicle. Levin said the clinical stage of drug discovery is expensive, so the team wanted a compound that met every requirement before moving toward people.

Why an on-demand option changes the conversation

Several other male contraceptives are in development, but they require a daily pill, a daily gel, or long-acting injections, according to the Cornell Chronicle. Those longer-acting products take weeks to become effective, and their effects on fertility may linger for weeks after a person stops using them, according to the Cornell Chronicle. The male contraceptive pill takes a different approach, since its effects wear off within several hours and a man can use it only when needed, according to the Cornell Chronicle.

Surveys cited by the Cornell Chronicle found that about half of men in the United States would use a male contraceptive, and that between one-half and three-quarters of men globally would do the same. Men surveyed also said a short-term, on-demand option appealed to them most, according to the Cornell Chronicle. That preference fits a wider shift in how younger adults talk about sex and prevention, including the changing attitudes described in recent reporting on Gen Z and solo sex and in peer-led sexual health programs that get more young people to use prevention.

The safety bar for the male contraceptive pill is high, because contraception is given to healthy people, often in their prime, Meinke said. The molecule has to act fast, stay potent, and remain safe, and it also has to keep stopping sperm from swimming after it reaches the female reproductive tract, Meinke said. Those demands explain why the team spent years refining the compound before seeking support for human testing, according to the Cornell Chronicle.

What happens next

The next step is developing an oral formulation of the drug, setting up manufacturing protocols, and evaluating safety in preparation for a first trial of the male contraceptive pill in healthy men, according to the Cornell Chronicle. Trial participants will receive the drug or a placebo and will be monitored for side effects, according to the Cornell Chronicle. Researchers will test sperm samples from both groups for motility, meaning the share of sperm that swim and how well they move forward, and they will verify that the immobilizing effect is temporary, according to the Cornell Chronicle.

Buck, Levin, and Meinke co-founded Sacyl Pharmaceuticals to support further drug development, and Gregory Kopf, the chief scientific officer at Sacyl, is leading the effort to turn the early discoveries into an approved drug, according to the Cornell Chronicle. The three founders hold equity and patents related to the technology, which Weill Cornell Medicine licensed to Sacyl, according to the Cornell Chronicle. Levin said sperm motility gives the team a strong biomarker for predicting whether the male contraceptive pill will work in people, and the current grant brings the compound to its first human trial.