A Case for Going Beyond Just Talking About Advancing Women’s Health: Let’s Take Action!

Authors:

Taryn Serman, Ph.D , Sr. Director of Communicationss & Research at Catalyst Healthcare Consulting, Inc.

Nancy Myers , CEO & Founder of Catalyst Healthcare Consulting, Inc.

Tara Croft , CEO of Baymatob

Sandy Milligan, MD JD , President of Aspira Women's Health

Lynne Yao, MD , Director of the Division of Pediatric and Maternal Health at FDA

At a recent the Drug Information Association (DIA) annual conference, we participated in an unusually insightful panel of women’s health experts who discussed why research into, innovations targeting, and investments supporting women’s health conditions are insufficient relative to their prevalence and severity. In this blog, we (1) summarize insights that emerged from our discussion, (2) exemplify the women’s health gap through case studies, and (3) outline potential steps forward.

Women’s health refers to sex-specific conditions that uniquely affect women (e.g., maternal and gynecological conditions) and general health conditions that affect women either disproportionately (e.g., many autoimmune diseases) or differently (e.g., colon cancer) than men.

Factors Limiting Innovation in Women’s Health

Our panel identified three key factors limiting innovation in women’s health that can be addressed with appropriate actions: 1) insufficient government–funded research, 2) a narrow band of companies innovating in the space, and 3) an immature investment landscape. Moreover, a historic lack of understanding of the unique physiology of women and hesitation around clinical testing on women of child-bearing age have compounded these factors.

To illustrate the three factors limiting progress in Women’s Health, we chose two representative health conditions, asthma and endometriosis, as comparative case examples to be discussed throughout this blog post. Both health conditions reduce the quality of life in patients that suffer from them, but neither are considered fatal diseases (though if left untreated, both can lead to serious complications). Asthma is an inflammatory lung disorder that affects men and women equally, while endometriosis is a chronic gynecological disease affecting only women. When applicable, we normalized the presented values by the prevalence of the disease in the US or the global population (i.e, divided the calculated values by the number of people with the respective disease in the US or across the globe).

Limiting Factor #1: Insufficient Government–funded Research

Historically, research on women’s health has been less prioritized and more staunchly underfunded relative to disease burden. In fact, basic research studies in female mouse models weren’t mandated until 2016. Moreover, a 2021 study found that out of all diseases that primarily affect one gender, NIH funded research for diseases that affect primarily men in 75% of cases, allocating only 25% of funding for those that primarily affect women.

Our case study analysis found that, when normalized to the respective US disease prevalence, the average annual US government funding over the last five years was four times lower for endometriosis compared to asthma. The on-average lower funding for endometriosis may partially explain why there were four times fewer research articles studying endometriosis published globally over the last five years compared to asthma, when normalized to the respective global disease prevalence (Figure 1).

Figure 1. Case Study Example of Lower Research Funding and Fewer Publications for a Women’s Health Condition compared to a General Health Condition. The averaged amount of government research funding over the last five years according to the NIH RePORT database was normalized to US disease presence. The number of research articles containing associated data published over the last five years according to a NCBI PubMed database search (criteria: “endometriosis” vs. “asthma”) was normalized to the global disease prevalence (Note: PubMed search was not US-specific). These values were used to calculate comparative values presented in the text and figure.?

Since prevalence isn’t the only factor governing whether research in a particular disease area is funded, we also compared US research funding amounts for prostate cancer, which affects only men, and uterine cancer, which affects only women. Our analysis found that uterine cancer received three times less research funding than prostate cancer over the last five years, normalized to US mortality. However, at least for this case example, the lower US funding did not correlate with the number of publications globally, normalized to global mortality (Figure 2).

Figure 2. Case Study Example of Lower Research Funding for a Women-specific Cancer compared to a Male-specific Cancer. The averaged amount of research funding over the last five years according to the NIH RePORT database was normalized to US disease mortality. The number of research articles containing associated data published over the last five years according to a NCBI PubMed database search (criteria: “(uterine) AND (cancer)” vs. “(prostate) AND (cancer)”) was normalized to the global disease mortality (Note: PubMed search was not US-specific). These values were used to calculate comparative values presented in the text and figure.?

Though these case studies are caveated by various factors beyond prevalence and mortality that affect funding and publication (e.g., affected population age), these examples illustrate the long-term effects of a historical lack of emphasis on women’s health research. A lack of funding means a lack of support to uncover the molecular and physiological mechanisms underlying a disease, ultimately preventing the discovery of novel therapeutic targets. Appropriate funding of women’s health research may lead to more pioneering findings that spawn more companies developing women’s health interventions.

Limiting Factor #2: Narrow Band of Companies Innovating in the Space

Companies innovating in the women’s health space are insufficiently represented due many factors, which include the historical lack of both women’s research funding and female inclusion in clinical trials, which wasn’t required in NIH funded-research until 1993. Today, it is clear that sex is biological variable underlying how disease and illness affect women and men differently and how they respond to treatments, leading to the current US Food & Drug Administration (FDA) policies guidances on inclusion of women in clinical trials. However, there are still barriers preventing sufficient enrollment of women in clinical studies, including under-diagnosing or not referring women to a study, unintentionally excluding women due to biologically–based study restrictions (e.g, BMI), and fear of harm if a woman becomes pregnant during the clinical trial. Moreover, in some cases, the historical lack of knowledge around physiological mechanisms underlying women’s health conditions has led to less established clinical endpoints and biomarkers for certain women’s health conditions. ??

Endometriosis is a good example of how lagging medical knowledge can affect clinical trials for developing therapeutics. Since endometriosis symptoms are shared with many other conditions, women must first have their endometriosis diagnosis confirmed via laparoscopic surgery and histopathologic diagnosis prior to enrolling in clinical studies. Moreover, since performing another laparoscopic surgery at the end of the trial isn’t feasible, endometriosis clinical studies have relied on patient-reported outcomes as endpoints. For drugs being developed that may potentially modify disease progression in endometriosis, development of validated biomarkers and definitive endpoints reflecting disease progression or regression would be of benefit because there currently are none.

These factors may partially contribute to why our case study analysis found there are more than two and a half times fewer interventional, currently-recruiting clinical studies and more than five and a half times fewer clinical trial results published in the last five years studying interventions for endometriosis compared to interventions for asthma (globally) (Figure 3).

Figure 3. Case Study Example of Fewer Clinical Trials and Less Published Clinical Data for a Women’s Health Condition compared to a General Health Condition. The number of global, interventional, currently-recruiting clinical trials according to clinicaltrials.gov was normalized to global disease presence. The number of clinical trial articles containing associated data published over the last five years according to a NCBI PubMed database search (criteria: “endometriosis” vs. “asthma”) was normalized to the global disease prevalence. These values were used to calculate comparative values presented in the text and figure.?

Our case study supports that the historical emphasis on health agendas other than women’s health research may have resulted in fewer pioneering discoveries underlying novel interventions, thus limiting progress in therapeutic development, reflected by the fewer number of active and published clinical trials.

Fewer companies innovating in the space and less supported clinical research may contribute to the approval of fewer therapeutic interventions, which is supported by our case study finding of a lower number of drug classes and individual drugs available to treat women’s health conditions compared to general or male-specific conditions, respectively (Figure 4).

Figure 4. Case Study Example of Fewer Therapeutic Options for Women’s Health Conditions Compared to General and Male-specific Conditions. According to drugs.com , there are 11 available classes of asthma interventions, compared to seven for endometriosis. According to cancer.gov , there are 42 available interventions for prostate cancer compared to nine for uterine cancer.

Fewer developers and approved therapeutics in the Women’s Health space means fewer success stories that may catch the eye of investors.

Limiting Factor #3: Immature investment Landscape

Ultimately, even if basic and clinical research catch up to spur more innovations, companies will have a very difficult time successfully developing novel women-specific therapeutic interventions without investor backing. However, despite the huge market potential, to date only 4% of all biopharma R&D spending in 2023 went toward women-specific conditions. ?This investor interest imbalance can be partially attributed to women making up only 12% of decision-makers at Venture Capital (VC) firms, as well as other inherent investor biases. Moreover, recent women’s health innovations have had relatively low returns on investment; for example, projected sales for Astellis’s menopause drug Veozah plummeted by 86% after launch due to slow uptake by payers and physicians. Big pharma’s recent retraction from women’s health– marked by Bayer shifting focus away from women’s health and Merck spinning out their woman’s health unit to Organon– doesn’t help the investor landscape. Ultimately, due to the historical lack of research and trials in women, the maturity of the investor ecosystem in women’s health is relatively young compared to other health conditions, meaning investors have small pockets and are wary of potential risks.

Our case study reflects the reported lack of investor interest in women’s health. According to the Fierce Biotech Fundraising Tracker, only one biotech company developing therapeutics for endometriosis (Freya Biotech) obtained VC funding ($38 million) in the last three years, compared to seven companies developing asthma treatments ($537 million). When these investment profiles are normalized to US disease prevalence and compared, two times less companies developing endometriosis interventions were funded with 15x fewer total funds in the last three years than for those developing asthma interventions (Figure 5).

Figure 5. Case Study Example of Less Investor Interest in a Women’s Health Condition Compared to a General Health Condition. The number of biotech companies that received VC funding from 2022-2024 was normalized to US prevalence of endometriosis and asthma, respectively. The 2023 VC funding of Freya Biotech intended to support four of their women’s health indications, one of which was endometriosis. For the purpose of this case study, we estimated that one-fourth of the funding went to the endometriosis indication, for a total of $9.5 million. We normalized the amount of calculated VC funding to US prevalence of disease for both endometriosis and asthma. ?These values were used to calculate comparative values presented in the text and figure.

Recent Progress toward Breaking Down all Three Factors Limiting Women’s Health Innovation

Decades of history can’t be undone in a single funding cycle, but recent initiatives have propelled Women’s Health to the forefront of medical and policy conversations. In November 2023, the Biden administration announced the White House Initiative on Women’s Health, which seeks to spur innovation in women’s health through $300 million worth of research funding, through both the Advanced Research Projects Agency for Health (ARPA-H) and the National Institutes of Health (NIH). Drug developers in the space know this is only a drop in the bucket, and that the whole $300 million could fund only one development program to registration and launch; however, the initiative did capture the interest of innovators since ARPA-H received an “unprecedented” number of proposals during the first call for applications. Beyond funding, the NIH Office of Women’s Health (ORWH) has an established Women’s Health Initiative and has recently published the 2024-2028 Strategic Plan for Women’s Health Research to advance research on women’s health conditions, foster women scientists’ career development, and advance community-engaged science across the research and healthcare continuum.

On the development side, regulatory agencies like FDA have the ability to ?significantly impact and encourage advancement women’s health. FDA has established the Office of Women’s Health (OWH)? to drive their Women’s Health Roadmap. Further, FDA has actively participated in NIH initiatives, like the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC), held educational Women’s Health webinar series, drafted guidance like the recent “Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies”. We look forward to hearing more and possibly participating in FDA’s OWH’s effort to update and advance the Women’s Health Roadmap.

In addition, groups like the The National Academies of Sciences, Engineering, and Medicine (NASEM) have contributed to dispelling unfounded perceived liability risks in conducting clinical trials on pregnant women, through reports like the “Advancing Clinical Research with Pregnant and Lactating Populations” published earlier this year.

But... There is Room To Do Much More To Fill the Gap

Investors are motivated by new science, understood targets, clear pathways to approval, and of course, large markets with needs. Despite a spike of interest in FemTech (digital technology focused on improving Women’s Health) in 20215, our perception is that investors are still waiting on the sidelines for Women’s Health to take off.? It will take more intrepid investors to establish? proof of concept that this field can support efficient innovation, produce profits, and is worth the risk of investment.

With the huge market potential and obvious need for health advances to treat half of the world’s population, a few well-targeted, effective actions and initiatives will likely bring the assurances ??investors need to recognize this field as a worthwhile investment.

Committing to Actions to Drive Change and Encourage investment

The recent funding, clinical trial advances, and published reports highlighting pathways to close the Women’s health gap have garnered widespread attention focused in on women’s health. It is critical that we continue to champion government investment in women’s health research, demand regulatory thinking that steps away from its paternalistic roots, and demand that momentum accelerates. Conversations like the one we hosted at DIA 2024 keep women’s health in the forefront of researchers’ and investors’ minds and serve to spur new ideas that may advance the space. For example, our panel discussion explored the idea of a Women’s Health Compensation fund that would financially reimburse patients experiencing adverse events from women’s health products to ultimately derisk the inclusion of women in clinical research. ?We need to have more conversations like these to continue generating fresh ideas while highlighting the obvious need and potential profitability of the women’s health field.

How can you help drive innovation in women’s health? Follow leaders in the field (like our DIA panelists Sandy Milligan, MD JD , Tara Croft , and Lynne Yao ), continue to encourage and support women in STEM and VC firms, get involved with women’s health nonprofits (like the Society for Women's Health Research (SWHR) ), and ?keep the conversation alive.

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