In the 1800s modern antibiotics didn’t exist, doctors were just starting to understand that tiny organisms caused disease, and X-rays wouldn’t become a reality until the very end of the century in 1895.
More than 100 years later, medicine looks very different, but one area of drug development remains the same — male contraception. Men today have the same two options that were developed in the 19th century — rubber condoms and vasectomy. But that may change over the next decade as researchers and companies move toward making pregnancy prevention more of a joint effort between men and women.
Today, nearly half of all pregnancies are unintended, and most of the burden for preventing them falls on women. Female contraceptive options range from hormonal pills, patches, rings, injections and implants, to barrier devices and IUDs — many of which come with a range of side effects, potential risks or just plain hassles.
For years, scientists have explored the idea of developing a male contraceptive. As many as 80% of men between 18 and 44 who participated in one survey said they are interested in preventing pregnancy, and many said they would be interested in a male option. But the search has been stymied by numerous factors.
One of the primary barriers is related to risk, said Lonny Levin, a professor of pharmacology at Weill Cornell Medicine, who is working to develop an on-demand male contraceptive.
“We’re going to give ourselves a year to get a better compound. Maybe we’re a little cocky but we’re pretty confident we can do that.”
Lonny Levin
Professor of pharmacology, Weill Cornell Medicine
“Contraceptives are very different than other therapeutics. They're not really therapeutics, they’re pharmaceuticals. But they're not fixing something, they’re taken by heathy people,” he said.
Unlike women, men don’t face risks related to pregnancy and childbirth. As a result, the bar is higher when it comes to accepting potential safety issues or side effects related to male contraceptives, Levin said.
There are also scientific challenges involved. For example, the average male produces around 1,000 sperm per second, according to the NIH. It takes around 74 days for sperm to grow and mature, so a contraceptive aimed at reducing sperm counts needs to work continuously starting more than two months ahead of time.
Over the years, there have been several attempts to create the male equivalent of “the pill.” However, as of yet, none have come to fruition. One experimental option, a two-hormone injection, successfully reduced sperm counts and appeared to be about 96% effective, but the phase 2 trial was halted due to side effects such as mood swings and acne. (Of course, both side effects are also commonly produced by many female contraceptives.) But several companies have continued the pursuit and are exploring new options.
A reversible male option
One particular effort was the result of a fortuitous discovery during unrelated scientific research. When Levin and Dr. Jochen Buck, also a professor of pharmacology at Weill Cornell Medicine, teamed up to study a cellular signaling protein called soluble adenylyl cyclase (sAC), they discovered that mice who lack this protein are infertile. Then Melanie Balbach, a postdoctoral associate in Levin and Buck’s lab made an additional discovery. She injected mice with a drug that inactivates sAC and found that it immobilized sperm.
Levin and Buck saw the potential for a contraceptive and are now testing a non-hormonal compound, TDI-11861, which they developed in conjunction with the Tri-Institutional Therapeutics Discovery Institute (TDI), a collaboration between the Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine. Their research, which is still in the preclinical stages, has found that this compound can temporarily put sperm to sleep, preventing them from traveling through the reproductive tract to fertilize an egg.
“What we're envisioning is a man would take the pill a half-hour before intercourse and he (would) have protection for a couple of hours,” Levin said.
Some men might consider the interruption and the 30-minute wait for the medication to kick in a drawback, Levin said. But a temporary form of birth control also has potential advantages, Levin said. Traditional hormonal contraceptives are typically taken daily, sometimes for many years or even decades, but this could be taken only as needed.
This on-demand formula could also improve trust between partners. The man would likely need to take the drug in a window of time when his partner would be present, eliminating the guesswork about whether he used the contraceptive correctly.
The race is on
Levin, Buck and another colleague, Gregory Kopf also launched Sacyl Pharmaceuticals to develop contraceptives.
“We appreciate that these next steps are important and that they're better done by an entity that has the flexibility of a biotech startup, better than an academic lab,” Levin said.
Sacyl’s work is backed by grants from the Male Contraceptive Initiative, which is aimed at funding male contraceptive R&D. The organization is also backing a number of other companies developing male contraceptives, including Eppin Pharma, a company also working on a compound to temporarily immobilize sperm. Their non-hormonal organic compound binds to a protein called EPPIN on the surface of the sperm to hinder its mobility.
Contraline Inc., a Virginia-based company, is also backed by the group and is working on a long-acting, but reversible contraceptive for men. The company is testing a hydrogel, called ADAM, which is injected into the vas deferens, the tubes that transport sperm. The sperm are blocked by the hydrogel and are reabsorbed by the body. Essentially, the procedure is a temporary vasectomy. The hydrogel is designed to liquefy in roughly two years, restoring fertility.
If these options, and others in the pipeline come to fruition, it would give men new options similar to what women have today — but more work needs to be done. Levin said they hope to bring their contraceptive to market within the next 10 years. Ideally, they’d like to improve on the compound they’re currently testing.
“We’re going to give ourselves a year to get a better compound,” Levin said. “Maybe we’re a little cocky but we’re pretty confident we can do that.”
In another year, he predicts they will be ready to move into pre-investigational new drug meetings. And if all goes as planned, he’s hoping the drug could make it to market in seven or eight years.
“We’re hoping that we can (get there) first,” he said.
