Birth control pills haven’t changed much since their inception in 1960, a state of affairs that Dr. Patricia K. Donahoe calls “almost medieval.” But if her more than 40-year quest to understand a little-studied hormone ends well, that could change.
Donahoe, director of Pediatric Surgical Research Laboratories at Massachusetts General Hospital, believes that the hormone, or drugs that mimic its effects, could slow or even halt the hundreds of eggs that women naturally lose every month — something that current birth control options cannot do. If true, the hormone could prolong fertility and potentially delay menopause.
On Thursday, biotech startup Oviva Therapeutics emerged from stealth mode to begin putting those ideas to the test with $11.5 million in seed funding from Cambrian Biopharma, a New York biotech focused on the biology of aging. Donahoe, her protégé David Pépin, and biotech entrepreneur Daisy Robinton cofounded the startup last year with exclusive rights to patents from Mass. General.
They think it is possible that drugs based on the hormone could act as a sort of anti-aging therapy for the ovaries, which age faster than other organs. “The idea is that with healthy ovaries, women may be able to stay healthy longer, and not suffer the consequences of menopause,” such as increased risk of osteoporosis and cardiovascular disease, Pépin said.
Therapies based on the hormone — called anti-müllerian hormone, or AMH — have never been tested in people, and as with any new drug, it will take years to prove that they are safe and effective for widespread use. But fertility doctors are already excited about the promise of turning the natural substance into a novel contraceptive.
“Scientifically, I think it is a solid idea and it’s long overdue,” said Dr. Vitaly Kushnir, an infertility specialist and medical director of West Coast Fertility Center in Fountain Valley, CA, who is not involved with Oviva, but has filed his own patents on AMH. “You could imagine a women in her twenties going on AMH-based contraceptive for 10 years, and then when she comes off it she has the ovaries of a 20-year-old rather than a 30-year-old. If it worked like that, it could be revolutionary.”
Kushnir himself has failed to muster investment in the concept. Soon before Oviva was founded, Donahoe and Pépin were “deep in negotiations” to develop AMH drugs with a pharma company, but the firm “didn’t see a large enough application for it,” Donahoe said. Pépin added that he has been told on more than one occasion “that women’s health is too political to invest in.”
Donahoe and Pépin’s luck changed when they met Daisy Robinton, 35, a scientist trained in the lab of Harvard Medical School dean George Daley. Her fascination with ovarian health began after she ended a long-term relationship when she was 31. Although Robinton knew other women who had struggled to conceive, until then she had never thought much about it herself.
So she began brushing up on her reproductive science. “I was horrified to learn that I knew very little about my own biology,” she said.
At the onset of puberty, a girl’s ovaries have about 300,000 follicles — small sacs that protect a single cell with the potential to become a mature egg. Every month, even if a woman is on birth control, she loses about 1,000 eggs. As the number approaches zero, menopause begins with its concomitant negative impacts on immunity, metabolism, sexual function, sleep, and more.
Existing birth control pills — based on the hormones estrogen and progesterone — prevent ovulation, the final stage in a follicle’s life cycle where an egg is released from the ovary to potentially become fertilized. AMH, in contrast, works much earlier in a follicle’s life cycle, pausing its development and thus preserving the eggs.
Curiously, Robinton said, no one ever talked about the ovaries at the longevity and anti-aging conferences she periodically attended. When Robinton noted this glaring oversight to James Peyer, founder and chief executive of Cambrian Biopharma, he was intrigued. Peyer invited her to join Cambrian in early 2020 to further explore the idea. “We didn’t know where it would go at that time, but it was such a powerful, interesting, and different thesis,” Peyer said.
Robinton was at Cambrian when she first heard of Donahoe’s and Pépin’s studies on AMH. One of the group’s experiments in lab animals suggested that the hormone may help prevent the loss of eggs and the early onset of menopause that is common in young women undergoing chemotherapy. Another study suggested that carefully timed use of AMH could improve the collection of eggs for in vitro fertilization.
That latter application — using AMH to help women struggling to conceive with IVF — will be Oviva’s first test of its AMH-based therapies in the clinic. Robinton views it as a “stepping stone to broader indications.”
Donahoe and Pépin have developed multiple strategies for turning AMH into a therapy, including one for manufacturing analogs of the natural hormone, which would likely have to be injected. They are also looking for small molecule drugs, which could be given as pills to mimic the effects of AMH. Robinton isn’t disclosing which strategy Oviva is focusing on, but said that all options are on the table.
Dr. Dror Meirow, a fertility doctor and AMH expert at Sheba Medical Center at Tel Hashomer in Israel, said the hormone could protect fertility in women undergoing chemotherapy, but using AMH in healthy people is “a completely different story.” He doubts that it will have as dramatic of an effect in healthy individuals, and warns that long-term use could disrupt the production of ovarian hormones and potentially cause, rather than prevent, the symptoms of menopause.
But Donahoe doesn’t believe that will happen. “The estrogen levels remain at a very healthy level,” she said. “We are not creating menopause.”
Other doctors welcome Oviva’s investment in women’s health, but say it is too early to get hopes up for an AMH-based contraceptive.
“It is an interesting and exciting idea, but it almost seems too good to be true,” said Dr. Laura Baecher-Lind, an obstetrician and gynecologist and director of women’s care at Tufts Medical Center. Even if AMH can preserve fertility, it won’t address the risks that accompany pregnancies later in life, she added. And she also doesn’t want people to fear menopause. “It is a completely healthy and normal part of life,” Baecher-Lind said.
Robinton acknowledges that some women look forward to menopause as a time to say goodbye to having periods or taking birth control. But for her, developing AMH therapies is all about creating more options. “My goal is for women to have more agency throughout their life,” she said. “And in this moment with Roe and the public policy landscape, it feels more urgent than ever to shout this from the rooftops.”
Donahoe agrees. “We think it is extraordinarily timely in terms of how reproductive choices are really under siege,” she said. “Having other options for reproduction couldn’t be more important.”