NIH Grant Funds First Human Trials of On-Demand Male Contraceptive Pill

Weill Cornell Medicine has received a four-year, $8.2 million grant from the National Institute of Child Health and Human Development (NICHD) to develop and test an experimental on-demand male contraceptive pill that temporarily stops sperm from moving. Dr. Jochen Buck and Dr. Lonny Levin, both professors of pharmacology at the institution, are leading the project, which aims to address a long-standing gap in reproductive medicine: contraceptive options for men remain limited to condoms and vasectomies, leaving the burden of pregnancy prevention largely on women, who often rely on long-term hormonal contraceptives that can carry side effects. Roughly half of all pregnancies worldwide are unplanned, a figure the researchers cite as evidence of an urgent unmet need.

The compound under development works by blocking an enzyme called soluble adenylyl cyclase, or sAC. According to the researchers, the pill would be taken about 30 minutes before sex and would provide a six-to-eight-hour window of protection from pregnancy, after which fertility would return to normal. Proof-of-concept studies funded by an earlier NICHD grant from the Contraceptive Development Research Center Program, published in Nature Communications in 2023, showed that inhibiting sAC rendered sperm immobile and prevented pregnancies in preclinical models. A second grant then supported the refinement and testing of different compounds to identify a candidate suitable for human use, a process in which Dr. Peter Meinke, assistant professor of pharmacology, contributed expertise in drug discovery and medicinal chemistry.

The new award is the third in the series and is intended to carry the program to its first human trial. It will fund the toxicology and safety studies required to demonstrate that the drug is safe for use in people, as well as the development of an oral formulation and the establishment of manufacturing protocols. The planned next step is a phase 1 placebo-controlled trial in healthy men, in which participants will receive either the drug or a placebo and be monitored for side effects. Sperm samples from both groups will be tested for motility, meaning the percentage of sperm that swim and how well they move forward, and the trial will also verify that the immobilization effect is temporary. The researchers note that sperm motility serves as a biomarker predictive of future efficacy, allowing the team to evaluate the compound’s long-term potential before larger efficacy studies.

The stringent safety requirements reflect the unusual nature of contraception as a pharmaceutical category. Because the medicine would be given to healthy people, often in the prime of life, Dr. Meinke explained, the candidate molecule must be fast-acting, potent and safe, active for hours in the male body, and still able to continue preventing sperm from swimming inside the drug-free female reproductive tract. Dr. Levin noted that the clinical stage of the drug discovery process is very expensive, which is why the team wanted to make sure it had what he described as a fantastic compound that checks all the boxes before moving into human testing.

The on-demand approach distinguishes this candidate from most other male contraceptives in development, which generally require taking a daily pill, applying a gel daily or using long-acting injections. Longer-acting products can take weeks to become effective, and their effects on fertility may linger for weeks after discontinuation, a pattern similar to many female hormonal contraceptives. An on-demand pill whose effects wear off within several hours would instead allow men to tailor contraception to individual circumstances. Survey data cited by the researchers indicate that about half of men in the United States, and roughly 50 to 75 percent of men globally, would use a male contraceptive, with respondents identifying a short-term, on-demand option as the most appealing format.

To advance the work beyond the laboratory, Drs. Buck, Levin and Meinke co-founded Sacyl Pharmaceuticals, Inc., where Dr. Gregory Kopf, the company’s chief scientific officer, is leading efforts to translate the initial discoveries into an FDA-approved drug. The three founders have licensed technology related to the research from Weill Cornell Medicine and hold equity and patents connected to the company and the technology, a financial interest disclosed in the announcement. Dr. Levin framed the long-term goal in terms of shared responsibility, expressing hope that family planning will one day involve men or couples obtaining male contraceptives at a local pharmacy, giving couples another option to discuss what works best for them. The immediate measure of success, however, remains the phase 1 trial itself: whether the compound proves safe in healthy men, whether sperm motility drops as the preclinical studies predict, and whether fertility returns to normal once the drug clears the body.

Subject of Research: Development and planned phase 1 testing of an on-demand male contraceptive pill that inhibits soluble adenylyl cyclase to temporarily immobilize sperm

Article Title: Weill Cornell Medicine receives NIH grant to test novel male contraceptive

Article References: Weill Cornell Medicine receives NIH grant to test novel male contraceptive. Original publication (Bibliographic details unavailable.)

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Keywords: male contraception, soluble adenylyl cyclase, sAC inhibitors, Weill Cornell Medicine, NICHD grant, phase 1 trial, sperm motility, on-demand contraceptive pill, Sacyl Pharmaceuticals, drug development, reproductive health, Weill