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 in their tracks. Dr. Jochen Buck and Dr. Lonny Levin, both professors of pharmacology at Weill Cornell, are leading the project to help fill an urgent global need for new contraceptive options for men.
Dr. Lonny Levin (left) and Dr. Jochen Buck
Currently, about half of all pregnancies worldwide are unplanned, and contraceptive options for men have been limited to condoms and vasectomies. As a result, the burden of contraception largely falls to women, who often rely on long-term use of hormonal contraceptives, which may have a variety of side effects, Dr. Levin said.
“We’ve developed an on-demand contraceptive pill that men would take 30 minutes before having sex,” said Dr. Buck. “The pill provides a six-to-eight-hour window of protection from pregnancy, and afterwards, fertility returns to normal. The grant will enable us to conduct the toxicology and safety studies needed to demonstrate the drug is safe for use in humans.”
This grant is the third in a series awarded to Dr. Buck and Dr. Levin’s shared laboratory. The long-time collaborators received their first grant from the Contraceptive Development Research Center Program at NICHD in 2020 to do proof-of-concept studies. The results of this research, published in Nature Communications in 2023, showed that blocking an enzyme called soluble adenylyl cyclase (sAC) rendered sperm immobile and prevented pregnancies in preclinical models.
The second grant funded refinement and testing of different compounds to develop a suitable candidate for humans. “The clinical stage of the drug discovery process is very expensive, so you want to make sure you have a fantastic compound that checks all the boxes,” Dr. Levin said.
Dr. Peter T. Meinke
Dr. Peter T. Meinke, assistant professor of pharmacology at Weill Cornell, has contributed his expertise in drug discovery and medicinal chemistry to optimizing sAC inhibitors into potential drug candidates.
“Contraception is unusual in that you're giving a medicine to healthy people, often in their prime, so the requirements for efficacy and safety are particularly stringent,” Dr. Meinke said. “You need a molecule that is fast-acting, potent, safe, and which is active for hours in the male but also continues to prevent sperm from swimming inside the drug-free female.”
The next step is moving toward a phase 1 placebo-controlled trial in healthy men, including developing an oral formulation, establishing manufacturing protocols and evaluating safety. “The current grant brings us to the first human trial of our drug and will allow us to evaluate its long-term potential,” said Dr. Levin. “We have a very good biomarker predictive of future efficacy—sperm motility.”
The participants will receive the drug or a placebo and will be monitored for side effects. Sperm samples from both groups will be tested for motility, the percentage of sperm that swim and how well they move forward. The trial will also verify that the immobilization effect is temporary. This will help confirm the drug is working safely as intended.
Several other male contraceptives are being developed but require taking a daily pill, applying a gel daily or using long-acting injections. Longer-acting contraceptives take weeks to become effective, and their fertility effects may linger for weeks after discontinuing the products, similar to many female hormonal contraceptives. The on-demand pills' mechanism of action allows men to tailor contraception to their needs since the effects wear off within several hours.
This video shows the motility of human sperm in the absence (left) or presence (right) of the experimental male contraceptive drug candidate. Credit: Dr. Melanie Balbach
Surveys have found that about half of men in the United States and about 50 to 75 percent of men globally would use a male contraceptive. Men surveyed also indicated that a short-term, on-demand option was most appealing.
“I hope someday family planning becomes a shared responsibility where men or couples can go to the local pharmacy to get male contraceptives,” Dr. Levin said. “This gives couples another option to discuss what is best for them.”
To support further development, Drs. Buck, Levin and Meinke co-founded Sacyl Pharmaceuticals, Inc. Dr. Gregory Kopf, chief scientific officer at Sacyl, is leading the effort to translate the initial discoveries into an FDA-approved drug.
Drs. Levin, Buck, and Meinke are founders of Sacyl Pharmaceuticals, Inc., which has licensed technology related to the research described in this article from Weill Cornell Medicine. Drs. Levin, Buck, and Meinke hold equity and patents related to the company and technology.
