From Intractable to Investable: Rethinking Clinical Development in Women's Health

Key insights from our Women's Health Symposium 2026

Laurel Woodridge (PhD)

Weatherden's Women's Health: From Intractable to Investable Symposium (11 June 2026, London) brought together senior leaders from biotechnology, pharmaceutical R&D, academia, investment and regulation to explore how applying smarter development strategies has unlocked investment in other therapeutic areas that were once considered commercially unattractive. Laurel (Data Science & Strategy Consultant) writes about the expert discussion from the event and how these principles can unlock innovation in Women's Health by accelerating investment to shape the next generation of therapies and improve patient outcomes.

Executive summary

Women’s Health has historically struggled to attract investment despite enormous unmet need – not because the science is impossible, but because we have been trying to solve the wrong problems. Despite being one of the most underserved patient groups in drug development, the challenges in developing therapeutics for Women’s Health are not new. Oncology, rare disease and metabolic diseases such as obesity faced similar problems: diagnostic delay, biological uncertainty, a lack of biomarker/validated endpoints, a lack of baseline data, and limited understanding of the long-term safety for chronic treatment. The next question is not whether innovation in Women’s Health is possible, but how the successful development strategies from these therapeutic areas can be translated. Building on discussions from a multi-stakeholder workshop involving regulators, investors, clinicians, academics and industry, this article proposes a practical framework centred on three priorities:

Better biology
Smarter endpoints
Stronger longitudinal evidence

Earlier collaboration with patients, regulators and investors together with better integration of clinical and real-world data - while addressing existing biases - can reduce uncertainty, build confidence and create more investable development pathways. While the inclusion of women, particularly pregnant women, in clinical research requires careful safeguards, the continued absence of evidence is itself a clinical risk that ultimately shifts uncertainty onto routine care that needs to be addressed.

The opportunity

The “Women’s Health gap” equates approximately to 24 million life years lost due to ill health. Across R&D, Women’s Health conditions (including cancers) make up only 5% of all spending whilst also representing an estimated $1 trillion market opportunity [1]. In over 4,000 clinical trial submissions between 2018-2023, only ~4% were female-only studies and only ~1% of these trials included pregnant or breastfeeding women [2]. These figures reflect more than historical under-investment and reveal a development ecosystem that has systematically generated less evidence for Women’s Health than other disease areas.

The consequences of these evidence gaps extend well beyond clinical trials. Excluding women from studies has not reduced clinical risk. It has instead shifted the uncertainty into routine care. Medicines continue to be prescribed during pregnancy, often with limited pregnancy-specific evidence, outdated safety information or off-label use. In effect, the evidence that could have been generated through carefully designed clinical studies is instead accumulated retrospectively through routine practice – where patients receive less intensive monitoring and far greater heterogeneity exists.

Risk assessment has historically focused primarily on potential foetal harm while giving less consideration to the clinical consequences of untreated maternal disease. For many chronic conditions, including autoimmune diseases, epilepsy, inflammatory bowel disease and psychiatric illness, discontinuing effective treatment may itself increase risks for both mother and baby. The relevant question goes beyond whether treatment carries risk, but which course of action carries lower overall risk. Where the choice is unclear, greater emphasis should be placed on informed decision-making rather than exclusion by default. Women routinely make complex healthcare decisions involving uncertainty throughout pregnancy. With transparent communication of what evidence is available – known risks and uncertainties – women may choose to participate in research. This is not an argument for lowering regulatory standards and passing the responsibility to the patient but recognizing that the absence of evidence is also a source of risk. Regulators should continue to prevent unacceptable or foreseeable harm with appropriate safeguarding and careful trial design to enable better evidence generation to support informed clinical decisions.

One of the main challenges to date has been a lack of regulatory precedent. Although regulatory approaches inevitably differ internationally, the U.S. Food and Drug Administration’s (FDA) early inclusion of pregnancy safety information in drug labelling suggests that progress is possible. The recent release of International Council for Harmonisation (ICH) E21 guidelines on the inclusion of pregnant women in clinical trials along with the Renewed Women’s Health Strategy for England [3] signals increasing regulatory momentum and a potential inflection point for the field. The National Institute for Health and Care Excellence (NICE) have also published guidance on the use of imaging in endometriosis [4] as another example of regulators actively enabling less invasive and more accessible pathways.

The question therefore becomes: which development strategies are most likely to close this evidence gap? Weatherden sought to identify the challenges, and more importantly the solutions, that could be strategically applied to conditions such as endometriosis, polyendocrine metabolic ovarian syndrome (PMOS), and menopause by bringing together key voices from across the ecosystem. Combining expert stakeholders – regulators, investors, academics/clinicians, pharma and biotech – we discussed the strategies that could be rationally applied to support development for Women’s Health conditions.

The take-home message from our workshop was that there is critical need for a holistic, multi-stakeholder conversation with parallel (not sequential) decision-making. Central to this hypothesis were three key themes that emerged where focused efforts will bring about genuine near-term success:

Better biology
Smarter endpoints
Stronger and more robust longitudinal evidence

Together, these themes represent a practical framework for translating proven development strategies from other therapeutic areas into Women’s Health.

Transferable lessons from other therapeutic areas

1. Better biology enables targeted therapies and biomarker/phenotype driven patient stratification

Substantial variability within patient populations complicates signal detection and a lack of defined subpopulations in conditions like endometriosis has hindered development. Breast cancer was once treated as a homogeneous entity but defined molecular biomarkers enabled classification of multiple biologically distinct diseases which require different treatment. This categorisation dramatically transformed outcomes and increased survival by ~44% over the last 50 years [5]. The principles underpinning oncology's biomarker-driven development provide a useful framework for Women’s Health.

The same principle extends beyond oncology: investment tends to follow biological confidence.

Deep mechanistic understanding creates new therapeutic possibilities by revealing tractable disease pathways and reducing uncertainty around target selection. For example, in obesity, elucidating the role of GLP-1 signalling in appetite regulation and energy homeostasis – combined with compelling clinical efficacy – transformed the field from once viewed as commercially unattractive to one of the fastest-growing areas of pharmaceutical investment. Likewise, defining the central role of B cells in autoimmune disease enabled the development of target therapies such as rituximab and belimumab, fundamentally changing the treatment paradigms across multiple conditions. Women’s Health presents a similar opportunity. Better molecular characterisation of diseases such as endometriosis, adenomyosis or PMOS, could reveal biologically distinct subtypes, enabling more precise patient stratification, rational target selection and greater confidence for regulators and investors [6].

Molecular phenotyping of Women’s Health conditions can only be enabled with more proactive approaches to basic science and clinical development. The current lack of validated preclinical models in Women’s Health conditions and male-centric studies has been structural reasons for the field's historic reliance on symptom treatment. This constraint is only now beginning to ease with the inclusion of female animals and cycling data. However, to enable this further, the additional time and expense associated with these changes needs to be baked into development timelines. Recent advances in analysis of primary cells from endometriosis patients has enabled the classification of cell types and identification of putative targets for disease modification – a significant step beyond prior reliance on symptom-based endpoints and a route towards identification of addressable patient subtypes that will enable better clinical development.

2. Smarter development pathways and better data

Clear and validated endpoints are critical for investment and a pre-requisite for capital commitment. Investors need confidence that endpoints will be accepted and reflect something that payers will reimburse. Likewise poor endpoint selection leads to downstream compliance failures and undermines real-world effectiveness. Rare diseases have demonstrated that regulatory uncertainty can be reduced through innovative evidence-generation strategies when conventional randomized trials are impractical. Integration of robust natural history datasets, registry-derived evidence and external control cohorts has enabled regulators to contextualize treatment effects and evaluate benefit–risk with greater confidence, supporting approvals such as onasemnogene abeparvovec (Zolgensma) for spinal muscular atrophy and establishing precedents for regulatory decision-making where conventional trial designs are not feasible. Sufficient convincing evidence led to regulatory acceptance and consequently investor confidence. Although many conditions affecting women are not rare, the lesson transfers: regulatory uncertainty can be reduced through smarter evidence generation, creating confidence needed to unlock investment and innovation.

In endometriosis, symptom severity does not map onto disease stage and therefore requires a smarter development pathway that integrates clinical, imaging (where invasive surgical measures are unfeasible), and histological classification. Where biology remains uncertain, clinical development itself can generate biological insight and help support curation of evidence, including the use of digital health technologies such as wearables (where appropriate) to better understand disease progression and treatment response without inflating development timelines.

Patient-reported outcomes (PROs) also play a pivotal role here whilst biological understanding is ongoing – identifying what patients want and designing trials and drugs according to unmet need. For example, PROs were instrumental in the approval of estetrol (E4)-targeting hormone therapy, Donesta® (Fylrevy), for the treatment of hot flushes in menopause. The unmet need was clear: to reduce the number of hot flushes. The addressable patient population was less interested in their oestrogen or progesterone levels, but convincing evidence came when symptom alleviation was directly linked to the underpinning biology and mechanism of action of the drug. Endpoints that women trust – that show a real-life benefit – will also help reduce potential attrition issues or recruitment failure and support long-term adoption beyond approval. Quality of Life scores/PROs must be incorporated as endpoints and when used alongside biological endpoints, PROs can accelerate evidence generation while ensuring therapeutic benefit aligns with outcomes that matter most to patients.

Beyond endpoint selection, women and patient advocacy groups should be engaged much earlier in clinical development. Their lived experience can help define meaningful outcomes, inform benefit-risk and help accelerate regulatory decision-making by providing evidence of unmet need and treatment value. However, this should be used to complement robust scientific and regulatory evaluation and regulators must continue to ensure that accelerated pathways are supported by sufficiently convincing evidence of efficacy and safety. Cautionary lessons are provided from the withdrawal of Biogen’s aducanumab whereby strong patient advocacy helped contribute to accelerated approval but cannot replace rigorous regulatory evaluation.

3. Adoption and long-term outcomes

For many therapeutic areas, post-authorisation evidence generation has become an integral component of the product lifecycle, helping to characterize long-term safety, effectiveness and treatment sequencing in routine clinical practice. In Women’s Health, however, the relative absence of long-term follow-up and baseline data represents a fundamental asymmetry in evidence priorities. Innovation in rare disease has demonstrated that regulators will accept novel evidence-generation strategies alongside clinical trials when conventional evidence alone is insufficient, including real world evidence and natural history studies which were successfully incorporated into regulatory submissions. Rather than replacing clinical trials, these complementary data sources strengthened evidence packages, informed label expansion and supported reimbursement decisions.

However, the challenges in Women’s Health are fundamentally different where many conditions are not constrained by small patient populations or limited opportunity for prospective data collection. Instead, large patient populations, regular clinical interactions and opportunities for longitudinal biological sampling remain substantially underutilized. Rather than creating disease-specific registries, future evidence generation should leverage interoperable health data infrastructure to establish a system where evidence is generated as a by-product of routine care. Embedding evidence generation within the healthcare would transform Women's Health from a series of disconnected clinical encounters into a continuous learning system. Linking electronic health records with imaging, laboratory data, prescribing records, pregnancy outcomes, biobank samples, genomics, digital health technologies and PROs would create a scalable evidence platform across life course while enabling repeated biological sampling and deep phenotyping at a scale rarely achievable in rare disease. Such longitudinal evidence could reduce uncertainty around safety, durability of treatment effect, sequencing and patient stratification, while supporting label expansion, biomarker discovery and sustained investment throughout the product lifecycle.

The opportunity extends beyond generating new data: Women’s Health is already supported by vast quantities of routinely collected clinical information that remain fragmented across healthcare systems. The challenge is therefore twofold: first, to better integrate, harmonize and critically evaluate existing data; and second, to build the infrastructure needed to ensure future evidence is captured systematically and consistently. Achieving this will require targeted investment into interoperable data standards and longitudinal evidence platforms, alongside continued efforts to address historical evidence gaps and biases through collection of high-quality, sex- and gender-disaggregated data. With representative and well-curated datasets in place, AI and advanced analytical methods can add genuine value by identifying biological subtypes, refining patient stratification and reducing – rather than amplifying – longstanding inequities in Women’s Health research.

Women’s Health should therefore be viewed not as a data-poor field, but as an evidence-rich field whose potential remains constrained by fragmented infrastructure, inconsistent evidence generation and longstanding inequities in data collection. With better use of existing evidence combined with prospective, representative data collection, Women’s health can evolve into a continuous learning healthcare system that generates the robust evidence needed to reduce uncertainty for patients, clinicians, regulators and investors.

The path forward

Women’s Health does not require an entirely new development paradigm. It requires adapting the proven playbook that transformed oncology, rare disease and metabolic disease. Better molecular characterization, clinically meaningful endpoints and continuous evidence generation have repeatedly reduced uncertainty, strengthened regulatory confidence and unlocked sustained investment in therapeutic areas once considered commercially unviable.

The challenge is not a lack of scientific opportunity, nor necessarily a lack of data, but integrating biological, clinical and real-world evidence to generate meaningful patient stratification, credible endpoints and long-term datasets needed to generate confidence for regulators, payers and investors.

Historically, Women's Health has suffered from fragmented incentives. Scientists sought biological understanding, regulators sought evidence, investors sought commercial certainty, and patient groups sought recognition - but these conversations often occurred sequentially in isolation rather than together. These challenges aren’t unique to Women’s Health and are visible in other underserved therapeutic areas. Progress in oncology and rare disease accelerated when these became integrated. Earlier collaboration between patients, clinicians, investors and regulators will be essential to define meaningful outcomes, generate the right evidence and build confidence throughout the development pathway.

References

Moley K. Closing the gender health gap is a $1 trillion opportunity. Nat Biopharma Dealmakers. 2024 May 20.
Manfrin A, Lee K, Pound J, Pirmohamed M, Raine J. Analysis of 4616 clinical trial initial submissions received by the Medicines and Healthcare products Regulatory Agency between February 2019 and October 2023. Br J Clin Pharmacol. 2025;91(9):2524-2533. doi:10.1002/bcp.70061.
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Efficacy guidelines [Internet]. Geneva: ICH; [cited 2026 Aug 4]. Available from: https://www.ich.org/page/efficacy-guidelines
National Institute for Health and Care Excellence. Our updated guideline to improve the diagnosis of endometriosis [Internet]. London: NICE; 2024 Nov 11 [cited 2026 Aug 4]. Available from: https://www.nice.org.uk/news/articles/nice-updated-guideline-to-improve-the-diagnosis-of-endometriosis
Giaquinto AN, Sung H, Newman LA, Freedman RA, Smith RA, Star J, et al. Breast cancer statistics, 2024. CA Cancer J Clin. 2024;74(6):417-438. doi:10.3322/caac.21863.
Koller D, He J, Løkhammer S, et al. Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations. Nat Genet. 2026;58:1051-1061.

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