Hunt for new non-hormonal birth control sends scientists under the sea

The material chitosan is used in wound dressings, hydrogels and even implants for nerve regeneration. Now, researchers want to add another application for the shellfish-derived compound to the list: birth control.

In a paper published Nov. 30 in Science Translational Medicine, a team led by Thomas Crouzier, Ph.D., of Sweden’s Royal Institute of Technology described how they developed a non-hormonal contraceptive that uses chitosan to reinforce the vaginal mucus barrier. When they tested the gel in eight ovulating sheep, only one of them was found to have sperm in its uterus after being treated—and in that case, just two sperm were detected.

“This study demonstrates the basis for a new mechanism of action for contraception. This would be the first one since hormonal contraception in the 1960s,” Crouzier told Fierce Biotech Research in an email. “This could mean topical reinforcement of cervical mucus could be the basis for a new class of contraceptives and finally provide a very desirable alternative for the millions of women wanting better non-hormonal alternatives.”

Crouzier was approached by an entrepreneur who had been researching the ideal contraceptive from the user perspective and was looking for a technology that could unlock it, he recalled. When the two met, “it quickly became clear that we could have a potential breakthrough if we apply the idea of mucus engineering to contraception,” he said.

In 2018, a company called Cirqle Biomedical was founded to take the product to development. The firm recently entered into a $360 million research collaboration and licensing agreement with Organon—a Merck spinoff focused on health and the maker of contraceptives Nexplanon and Nuvaring—to finish preclinical studies with the goal of moving into clinical trials, according to Crouzier. 

While women have no shortage of hormonal birth control options—from pills to shots, patches, and devices such as intrauterine devices (IUDs) and rings—there are far fewer non-hormonal contraceptives. Some of them, like spermicide, are much less effective. Spermicide’s efficacy rate is around 76% when used alone, compared to between 95 and 99% for the pill when used correctly.

CooperSurgical Inc.’s copper IUD ParaGard boasts a 98 to 99% efficacy rate if inserted at least five days before unprotected sex. But non-hormonal doesn’t necessarily mean without side effects. ParaGard can cause cramps and heavy periods. It also must be inserted by a gynecologist, which can be expensive or inconvenient for those who can’t afford to take time off work.

The newest addition to the non-hormonal line-up is EvoFem’s Phexxi, a contraceptive gel with an efficacy rate of about 86%—roughly the same as condoms. Approved by the FDA in 2020, Phexxi works by keeping the vaginal pH at a level that makes it difficult for sperm to travel to and fertilize an egg. It’s designed to be inserted by the patient immediately or up to a few hours before intercourse.

The contraceptive gel developed at the Royal Institute of Technology is designed to be injected into the vagina as well, but works through a different mechanism of action. Outside of ovulation, cervical mucus already blocks sperm from entering the uterus. During ovulation, it becomes more watery, allowing them to pass.

“The idea was quite simply that instead of adding a barrier like a diaphragm, we could potentially leverage nature's own barrier—cervical mucus,” Crouzier explained. “By reinforcing the natural barrier property of cervical mucus it could be possible to prevent sperm cells from reaching the egg.”

It’s thought that progesterone-only birth control pills, also known as the mini-pill, work in part by strengthening the cervical mucus barrier as well.

Cervical mucus is composed of mucin molecules. The gel cross-links these with chitosan, thickening the mucus and making it more difficult for sperm to pass. When sperm were exposed to the gel in lab experiments, they were partially blocked within one minute and completely blocked within five. The gel is designed to be gradually removed from the vagina via the same mechanisms as natural cervical mucus.

This isn’t the first time scientists have attempted to develop topical products to strengthen cervical mucus, but such projects have been rare and unsuccessful, Crouzier said. Part of the problem was a relative lack of investment in the field.  

“The lack of funding and lack of talent working on these problems have kept the chance of discovering new non-hormonal methods relatively low,” he explained.

Next, the lab is working on elucidating any potential side effects from the gel. The likelihood of adverse effects is low given its mechanism of action and chitosan’s track record of use in biomedical applications, but such studies will be important nonetheless, Crouzier said. The material is derived from the shells of crustaceans like shrimp and lobster and has many medical and agricultural uses.

“A new contraceptive should be safe and effective,” he said. “We believe the technology has the potential to be both, but there is a long road ahead to demonstrate this clinically.”