Endometriosis drug research is chronically underfunded, facing common dilemmas in women's health

Allie Shortt was diagnosed with endometriosis at age 12, when she felt alone. With limited treatment options and scarce information, she and her family had to teach themselves to become medical researchers.

Even the diagnosis itself came about because Shortt's mother connected the pain she was experiencing to symptoms described by women in a patient organization.

"What ultimately convinced my parents I had this disease was seeing and reading about other people's experiences and recognizing that I had gone through something similar," Shortt said.

In some ways, Shortt's case is rare. Her diagnosis came early, while some women may go a decade or more before learning they have endometriosis due to poor disease awareness, misdiagnosis, or the bias that severe menstrual pain is normal.

"If you think something is supposed to be uncomfortable, it's easy to dismiss someone else's discomfort," said Sommer Babrick, CEO and co-founder of Hera Biotech, which is developing a non-surgical diagnostic tool for endometriosis.

Endometriosis is caused by uterine tissue growing outside the uterus, often affecting menstruating people but can also occur in postmenopausal women. The disease is characterized by chronic pelvic pain, especially during menstruation, but can also cause problems in other parts of the body. It is often diagnosed via laparoscopy because ultrasound does not always show abnormal tissue growth.

Although doctors' understanding of the disease has improved, the root cause of endometriosis remains debated, even though it affects about 10% of women and girls globally.

"(Endometriosis research) has been underfunded, so despite the disease being common, it's not well understood," said Marina R. Walther-Antonio, a surgical assistant professor and microbiome researcher at the Mayo Clinic in Minnesota.

When Shortt was diagnosed, there was little she could do—a reality that frustrated her and her family. "I just felt like I finally had an answer, and if we knew what the problem was, there would be a solution," she said. Even so, since then, only two new drugs have been approved in the U.S. for endometriosis-related pain.

This pattern is typical in diseases that primarily or exclusively affect women, such as endometriosis. Underfunding of women's health research has suppressed the development of new products, leaving common conditions with few treatment options. Although clinical trials are more inclusive than in the 1990s and earlier, research does not always reveal why or how disease symptoms differ by biological sex.

Missing information

For any disease, drug development is no easy task. But when the disease itself is not well understood, the process is more difficult, as is the case with endometriosis.

"We face multiple deficiencies, one of which is a lack of information," said Hera's Babrick. "I think that's a struggle for all founders in women's health."

For example, researchers sometimes use biobanks—collections of medical and biological data including tissue, blood, and DNA samples—to identify molecular markers of diseases or develop effective diagnostics. If collected by government-funded projects, the data is often published or made available to scientists, providing a starting point for drug research.

But Babrick and Joseph Nassif, an associate professor of obstetrics and gynecology and clinician at Baylor College of Medicine, say such resources are more limited in the endometriosis field. While other countries are more advanced in this research, the U.S. is just getting started.

"So right now in the U.S., we're trying to build a database of all (endometriosis) patients," Nassif said. "We have cancer banks and banks for other diseases. Once we have a large number of patients, we can study it better."

With a weaker foundation, drug developers targeting endometriosis or other women's health conditions like polycystic ovary syndrome or premenstrual dysphoric disorder may find it harder to get started.

"When you build your company's 'data story,' your story looks weaker than companies focused on indications outside women's health because they have access to all these resources," Babrick said.

This lack of information has deep roots. Until 30 years ago, the U.S. Food and Drug Administration (FDA) recommended excluding women of childbearing age from Phase 1 and 2 clinical trials, even if they used contraception. These policies were a response to birth defects caused by thalidomide, a drug used to treat nausea in women in the 1950s and 1960s.

A 1993 law mandated the inclusion of women and minorities in NIH-funded clinical research, but the impact of discouraging women from participating in trials persists.

For example, a 2022 study found that women made up 41% of participants in Phase 1 to 3 trials of drugs and medical devices conducted in the U.S. between 2016 and 2019. Compared to the estimated proportion of women among patients with many diseases like heart disease and mental illness, women are underrepresented.

Shortt said these research gaps and the resulting lack of knowledge ultimately put "the lives of girls, women, and their families" at a "significant disadvantage."

The federal government has tried to make up for it. Most recently in February, the Biden administration pledged $100 million for women's health research. The FDA also recently updated draft guidance to ensure sponsors conduct more diverse clinical trials, supporting the 2022 Food and Drug Omnibus Reform Act, which requires specific documents and strategic plans.

"When you're trying to understand a drug's effectiveness, tolerability, and safety, it's important to test it in a population representative of those who will use the product," said Katherine Seay, head of sales and operations at Clinical Trial Media, a patient recruitment and retention company.

Limited options

Compared to other areas of drug development, women's health remains underfunded. An analysis of NIH-funded research found that diseases primarily affecting men received more funding. The major women's diseases that do receive investment are often concentrated in oncology, such as breast and ovarian cancer, and reproductive medicine.

For example, Babrick did not intend to make reproduction the focus of Hera. But it was only when she mentioned the negative impact of endometriosis on fertility that the company attracted investor interest. "While our reproductive organs may be involved in these chronic diseases, our fertility shouldn't be the focus," Babrick said.

Hera's struggle for attention is not unique. Despite the prevalence of endometriosis, it remains low on the radar of pharmaceutical companies.

Women with the disease often take birth control pills, other hormonal therapies, and painkillers to manage symptoms and menstrual cycles. They may also turn to surgery, either to remove lesions caused by endometriosis or, in severe cases, to completely remove the uterus.

When Shortt was young, the drug Lupron Depot—a hormonal therapy originally used for prostate cancer—was approved in the U.S. for managing endometriosis-related pain. The drug can cause menopause-like side effects and was a "terrifying" experience for Shortt, who was about 13 at the time.

In the past decade, the FDA approved two other products for endometriosis pain management: AbbVie's Orilissa (2018) and Pfizer and its partner Myovant Sciences' Myfembree (2022).

These drugs are not cheap: both Orilissa and Myfembree are priced at over $1,000 per month. They also do not address the root cause of the disease and are limited to up to two years of use due to the potential for decreased bone density.

"These options aren't widely discussed or promoted because they don't really treat the disease," Babrick said. "They just quiet some symptoms that make your life unbearable, but then you run into a host of other symptoms that can be just as unbearable."

Shortt was prescribed Myfembree as an adult but never took it due to its limitations and potential impact on bone density. She said she likely wouldn't take Orilissa for the same reasons.

"Currently, we have ways to manage (endometriosis), whether it's medication or surgery, and certainly there are success and failure rates," Nassif said. "But definitely, we need a lot of research in the future."

Sparse pipeline

Neither Orilissa nor Myfembree are blockbusters, and they seem to rank low in their manufacturers' priorities.

Three years after Orilissa was approved, AbbVie tried to sell the women's health unit that housed the drug, but the deal never materialized. Sales of the drug are no longer reported separately but are folded into "other key products" in AbbVie's earnings. AbbVie last reported Orilissa's net revenue in fiscal 2021, when U.S. sales were $139 million.

AbbVie did not provide more details about the drug's development or sales when contacted by BioPharma Dive.

In 2022, Japan-based Sumitomo Pharma agreed to acquire Myovant Sciences, the developer of Myfembree, for $2.9 billion. The drug is now sold by Sumitomo in Europe, while Pfizer co-markets it in the U.S. and Canada.

Pfizer does not report net sales but lists Myfembree revenue as a contributor to "alliance revenue" in financial filings.

These two drugs face little competition. Women's health company ObsEva had licensed a compound called linzagolix from Japanese biotech Kissei Pharmaceutical. However, after the FDA told it that its submission was flawed, the company terminated the deal and withdrew its approval application.

ObsEva ceased operations earlier this year, one of several women's health companies that have had to adjust their research focus recently.

Pharmaceutical company Bayer has long sold a hormonal drug called Visanne for endometriosis-related pain, but the company has not filed for approval of that indication in the U.S.

"We focus our research efforts on innovative options for areas of high unmet medical need," a Bayer spokesperson said in comments to BioPharma Dive. "We regularly review our R&D portfolio to prioritize the most promising programs."

Bayer also collaborated with U.S. and British researchers to help identify an inflammatory gene that may be linked to endometriosis. While the finding seemed to point to a possible non-hormonal drug target, further research "ultimately did not progress into development," according to the Bayer spokesperson.

Last year, Bayer completely shifted its research focus away from women's health. While new R&D could still yield women's health products, Bayer executives told Reuters that the company's overall work in the area "did not meet expectations."

Elsewhere, Organon agreed in 2021 to acquire Forendo Pharma for a $75 million upfront payment, gaining a candidate drug that targets endometriosis lesions without affecting hormones. Other startups have also emerged, including Gynica, FimmCyte, and SLBST Pharma.

Looking ahead

While endometriosis research continues, Babrick believes finding non-hormonal targets to treat the disease must become a priority.

"We have to understand (endometriosis) mechanistically so we know which levers to pull and which knobs to turn," she said. "So, there needs to be more research on the mechanism side."

There is some progress now. In addition to the Biden administration's $100 million pledge for women's health research, the Advanced Research Projects Agency for Health (ARPA-H) has launched a "Women's Health Sprint" to fund health solutions that primarily or disproportionately affect women.

However, it is unclear whether these efforts will remain a priority under President-elect Donald Trump's administration. Trump has nominated Robert F. Kennedy Jr. to lead the Department of Health and Human Services, which oversees health agencies including the FDA. While Kennedy has been vocal about his views on vaccines and the pharmaceutical industry, his views on women's health research are less clear, and his stance on abortion has been inconsistent.

At a rally before the election, Trump said Kennedy is "very focused on women's health" and would let him "go wild on healthcare."

Some experts worry that state abortion bans could hinder recruitment for trials involving in vitro fertilization or other procedures that may require documenting a woman's medical history.

"I think once you take away a woman's freedom of choice and put it in the hands of politicians, whether at the state or federal level, it's not a good thing," Shortt said. "It will have far-reaching effects that may go beyond what we can currently understand, and I do think it involves endometriosis."

Amid these concerns, there is still hope for progress in treating endometriosis. However, Babrick said sustained interest and investment will require "a concentrated effort to highlight, educate, and bring attention to the issues or consequences of being a woman."