Key takeaways

• Even when women’s health therapies win FDA approval, they often fail to achieve broad payer coverage because their clinical trials weren’t designed with access in mind.
• The most important access decisions that determine reimbursement success often happen during trial design, not during payer negotiations.
• The most successful programs align R&D leaders and market access teams early to design evidence that supports both approval and coverage.

Women’s health R&D continues to generate regulatory approvals that underperform commercially, even though closing this gap could unlock $1 trillion in annual global GDP. Women spend 25% more of their lives in poor health than men, yet just 7% of biopharma R&D targets conditions with women-specific indications, and less than 1% of that goes to conditions unrelated to oncology. Even when they do win FDA approval, women’s therapies often underperform due to a lack of practical and durable reimbursement coverage. Typically, the evidence gaps responsible for this are visible before phase 3 of a trial begins.

Let’s explore why and what needs to change.

Who in pharma can solve the evidence gap in women’s health?

No single function owns this problem, and no single function can solve it alone. Our focus is on two audiences who rarely read the same documents: the R&D leaders who design and fund trials and the market access leaders who inherit the evidence those clinical trials produce. Closing the gap starts with these two functions working from a shared view of what “successful” evidence looks like, from the earliest stage of trial design.

What R&D leaders can do to advance women’s health

If you design and fund clinical trials, the commercial consequences of trial design decisions may not be fully visible to you. The evidence gaps that block reimbursement do not happen at launch, they happen in the protocol. Phase 3 is where access outcomes are solidified, not where they are discovered. Our analysis traces what happens downstream based on the decisions you make upstream.

What market access and commercial leaders can do to advance women’s health

If you manage a reimbursement strategy, you likely inherit evidence packages you had no hand in designing. The coverage restrictions and payer friction you navigate at launch were largely determined years earlier by comparator choices, enrolled populations and subgroup analyses that were built into the design or left out. The levers that matter most for access are pulled in R&D, not in the payer negotiation.

What’s causing the evidence gap in women’s health?

Increasingly, women’s health drugs are getting approved but they are too often not achieving favorable payer coverage.

ZS analyzed dozens of women’s health approvals from the last five years, examining trial design, payer coverage from launch to today and commercial success. Six launches in particular shed light on the challenges of designing for approval, not access, while two launches show what designing for women from the beginning could look like.

While each product’s situation was unique, we identified three key learnings that contribute to the gap in women’s health coverage.

Clinical trials remain male-centered: Women aren’t represented

Despite efforts to include more women in clinical research, they still aren’t participating in trials as often as men. Fewer than 34% of phase 1 participants from 2013 to 2015 were women. More than 98% of medications have insufficient data to guide dosing in pregnancy or breastfeeding, yet more than 80% of pregnant patients receive them. This leads to:

• Dosing calibrated to male pharmacokinetics
• Sex-specific adverse events masked in aggregate data
• Label restrictions that become immediate coverage barriers at launch

Trials exclude the patients payers care about most

Recruitment designs tend to be concentrated in academic medical centers. Scheduling demands are often incompatible with caregiving responsibilities. Breastfeeding women are routinely excluded. These structural barriers bias enrolled populations to not reflect the people who would use these treatments in the real world. When coverage analysts see a breastfeeding exclusion in a postpartum depression trial, they respond through prior authorization requirements. This restriction is a direct response to the protocol written years earlier.

Payer requirements enter the conversation too late

The dominant development framework, the Target Product Profile, is built around regulatory requirements. It may not ask what evidence payers need. When payer engagement happens at the launch stage, the evidence is already locked.

Payers don’t invent new requirements at launch. They apply frameworks that already exist before phase 3 starts: comparative effectiveness data, powered subgroup analyses and classification of the condition as a disease state rather than a quality-of-life concern. These are known requirements that should be built into trial design to produce the required evidence.

6 underperformers and 2 successes in access to therapies for women

Across the approvals we examined, regulatory success did not predict commercial access. In the underperforming cases, the evidence gaps that blocked reimbursement were visible before phase 3 enrollment began. We walk through the underperforming cases here to identify the specific design decisions that produced poor access outcomes, not to criticize the sponsors involved. In most cases, the evidence gaps that drove reimbursement failure were predictable from the structure of the trial, not from hindsight.

Underperformers in women’s therapies

Zulresso (brexanolone)

This was the first drug built specifically for postpartum depression, and it was effective. But the therapy required a 60-hour infusion in a certified healthcare setting under a REMS program. This led to treatment delays and extended time in the hospital, neither of which was conducive to treating new mothers. It reached just 499 patients before being withdrawn in 2025. The science succeeded. The delivery format made it unprescribable.

Zurzuvae (zuranolone)

Zurzuvae, an oral treatment for postpartum depression, overcame the delivery problem that killed brexanolone, but had a similar breastfeeding data gap and lost its broader depression indication when the evidence was insufficient. The treatment then faced repricing issues after payers had already locked in restrictive coverage terms.

Veozah (fezolinetant) and Orilissa (elagolix)

Veozah treats moderate-to-severe hot flashes caused by menopause. Orilissa treats moderate-to-severe endometriosis pain. Different indications, same challenges: Both launched without a head-to-head trial against the standards of care they were meant to replace. Payers had no basis to prefer either. Step therapy became the default, and both drugs were pushed behind older, cheaper options.

Osphena (ospemifene) and Intrarosa (prasterone)

Both drugs treat moderate-to-severe dyspareunia (painful intercourse) caused by vulvovaginal atrophy due to menopause. Years after launch, both still face coverage friction. Payers classify the indication as a quality-of-life concern as opposed to a health condition, creating an access problem that trial evidence alone can’t fix.

Makena: The highest-stakes case

Makena (17-alpha hydroxyprogesterone caproate), indicated for the prevention of recurrent preterm birth in women with a history of spontaneous preterm delivery, achieved approval, broad coverage and widespread adoption. But it collapsed when its confirmatory trial enrolled 89% white participants, with 61% recruited from Russia and Ukraine. Black women, who experience preterm birth at nearly twice the rate of white women, were barely present in the confirmatory trial—even though they were well-represented in the original approval trial. When the evidence failed to hold, the women who needed this support most lost their only approved treatment. More than $700 million in spend was lost.

Successes in women’s therapies

Renovia’s Leva digital therapeutic

Renovia converted its Leva pelvic health trial to a fully virtual design, built around how patients live rather than around site logistics. The result: 95.7% retention in a population that matched real-world users more accurately than any conventional site-based study would have achieved. Cigna added Leva as a covered, “medically necessary” treatment in 2023, access that had been inconsistent up to that point.

Novartis’s PARAGON-HF trial

The PARAGON-HF trial prespecified a sex-specific subgroup at the design stage, before enrollment began. That single decision found a significant benefit in women with heart failure with preserved ejection fraction and earned an FDA label expansion for Entresto, which could make up to 1.8 million more patients eligible for treatment. The commercial upside resulted from the sex-specific design.

5 questions to ask before phase 3 of your clinical trials

After analyzing what determines success and failure in women’s health R&D, we found that these trial design decisions separate programs with durable access from programs that stall at launch. Answer these questions before the protocol is locked.

Evidence

1.  Does your payer evidence plan match your clinical trial design?

What comparative effectiveness data, subgroup analyses and population inclusions do payers require? Are these requirements accounted for in your protocol? If a structured payer advisory conversation hasn’t taken place, the answer is probably no. Is your payer advisory board happening too close to launch to apply critical feedback? Building an integrated evidence plan, supplemented with real-world evidence, health economic modeling and more can make a huge difference.

2.  Have you engaged payers on how your condition is classified?

Disease state or quality-of-life? That classification determines the evidence threshold, the cost-effectiveness framework and the default coverage logic. It is negotiable before evidence is locked and largely not after.

Population

3.  Is your enrolled population the population that will use this drug?

Who bears the greatest burden of the condition you’re treating? Are those women represented in your trial? If enrollment speed is what drove site selection, the populations most affected are likely underrepresented.

4.  Have you prespecified sex as a primary subgroup variable?

The Entresto expansion was possible only because the sex subgroup was prespecified. A retrospective analysis would not have unlocked the label. If your indication has a sex-specific signal, your trial needs to be powered to detect it.

Delivery

5.  Is your delivery format compatible with the real lives of the women you’re treating?

Brexanolone’s 60-hour infusion requirement was foreseeable as an issue from day one. It is becoming standard practice to have patients validate trial design and therapeutic details to understand future feasibility and uptake. Does the administration mechanism your trial is testing actually work for the patients who need it?

The upside is real: Investing in women’s health matters

Endometriosis—it’s an estimated $180 to $220 billion global market. Menopause is estimated at $120 to $230 billion. Both rival cardiovascular and respiratory markets, and both receive a fraction of the industry’s investment. Across the conditions disproportionately affecting women, Women’s Health Access Matters (WHAM) estimates a $360 billion global “ghost market” is sitting unaddressed. For every $1 invested in closing the women’s health gap, there is potential for approximately $3 in economic returns.

Capital is already moving. Venture investment in women’s health grew 55% in 2024 alone, adding roughly $1 billion in new funding to the space. The market has priced in the opportunity. What’s missing isn’t capital or demand. It’s the evidence designed to convert that demand into coverage.

What will make a difference? An access-oriented R&D model for women’s health that integrates both payer needs and women-centered trial design. To succeed, this model must be in place at the start, and trials must include the populations that will actually use the therapy. The Entresto expansion is just one example, driven by one prespecified sex-specific subgroup analysis that made 1.8 million more patients newly eligible for treatment. This is the true potential of access-oriented design.

Here’s more on why ZS is committed to helping clients advance women’s health.