Article | June 14, 2024

Partnering To Address 'Huge' Opportunities In Women's Health

Source: Life Science Leader
Ben Comer_2022_1

By Ben Comer, Chief Editor, Life Science Leader

Womens health feature

Women’s health as a target area for research and drug development has momentum across the biopharma industry, and for good reason. Big Pharma, biotech, diagnostic developers and digital health startups increasingly recognize the gaps and unmet needs in diagnosing and treating not just diseases related to pregnancy and childbirth, but also discrepancies in therapeutic outcomes across myriad disease states, from neurological disorders to cancer and cardiovascular disease.

The opportunity is immense; investments addressing the women’s health gap could potentially boost the global economy by $1 trillion annually by 2040, according to a World Economic Forum and McKinsey Health Institute report. Women — despite living longer than men on average — spend 25% more of their lives in debilitating health. Due to historical inequities in clinical research, less is known, and less data is available, regarding treatment outcomes in diseases disproportionately affecting women such as Alzheimer’s and multiple sclerosis. Studies have shown that women are also more likely to die from a heart attack than men.

What is needed is a transformation in clinical research and treatment to enable sex and gender precision medicine, says Dr. Antonella Santuccione Chadha, Ph.D., CEO and cofounder of the Women’s Brain Foundation. “As more drug developers start to understand the huge opportunity around women’s health, we’re going to get better drugs.”

Before the passage of the NIH Revitalization Act in 1993, clinical trials were not required by law to include women as a prerequisite to receiving NIH funding. And during the late 1970s and early 1980s, the FDA actively recommended excluding women of childbearing potential from participating in Phase 1 and Phase 2 trials, a crucial period for understanding pharmacokinetics: how a drug substance is absorbed, distributed, metabolized, and excreted by the human body. Without the participation of women, sex and gender differences related to the safety and efficacy of new therapies can not be adequately understood.

In the FDA’s defense, an important reason for female exclusion from early-stage clinical studies at that time was the agency’s desire to protect women and unborn children from harm. After the tragedy that thalidomide wrought – a sedative developed without the inclusion of pregnant women and marketed globally during the 1950s and early 1960s, leading to thousands of birth defects and deformities – the FDA, which rejected approval in the U.S. over safety concerns raised by agency staffer Frances Oldham Kelsey, kept women out of clinical trials as a safeguard.

The unfortunate result of that well-meaning approach to safety is that “women’s health as a field is only about 30 years old,” says Michael Annichine, CEO at Magee-Womens Research Institute and Foundation, referring to the passage of NIH Revitalization Act. “To this day, only about 13 cents on the dollar gets invested in women’s health.”        

Nonprofit Partnerships To Improve Women’s Health

Michael Annichine
Michael Annichine
Magee-Womens Research Institute and Foundation, based in Pittsburgh, PA, regularly works with life sciences industry partners to improve the safety and efficacy of existing products used by women, and to help bring new drugs and diagnostics to market. At any given time, Magee-Womens is involved in roughly eight to 10 projects with life sciences companies, says Annichine. Recent or existing project partners include Merck, Pfizer, Genentech, Organon, Bayer, Boston Scientific, and Philips. “One of the big things we do really well here is drug reformulation,” says Annichine. “It is well documented that certain drugs metabolize very differently in the female body.” Ambien, a sleep aid, is one example of a drug with significant sex-based variation; at equivalent dosages, women are more likely than men to face increased risks of impaired driving, for example, the morning after using Ambien.

Annichine offered three examples of how Magee-Womens partners with life sciences companies to improve women’s health:

  • Preclinical research support for drugs to be used by pregnant women. “We have biobanks and databases at Magee-Womens that allow us to do preclinical work with a significant amount of expertise,” which individual biopharma companies may not have in house, says Annichine. That capability helps developers build a drug safety profile before going into human clinical trials that might include pregnant women.
  • Patient cohort segmenting and analysis. Clinical researchers testing products in diverse populations often find variations between different patient groups, including sex-based differences. Drug developers work with Magee-Womens to investigate the reasons behind those differences to better refine trial inclusion criteria, or to explore additional indications.
  • Responding to safety signals or adverse events. In situations where a drug demonstrates efficacy in clinical trials or in the market, but also produces unwanted side effects, Magee-Womens can help to “refine or reformulate a drug” for a specific patient population, such as women, per Annichine.

In disease areas specific to women or reproductive health, such as endometriosis, Magee-Womens is working on better diagnostic testing to prevent the quixotic patient journey many women experience. “Endometriosis takes 11 years and eight different doctors on average to diagnose,” says Annichine. “Because of that, the market size for that disease is undervalued and underappreciated. People are starting to realize what the size of those markets could be if we had better diagnostic testing.”  

Annichine’s message to the biopharmaceutical industry is a simple one: Magee-Womens is open for business. The Magee Obstetric Maternal and Infant (MOMI) database and biobank goes back to 1995 and contains data from over 220,000 pregnancies, with clinical information from 10,000 deliveries added every year. MOMI is “the largest database of its kind in the world,” and the organization also maintains a “large tumor biobank collected over many years,” says Annichine. “We are happy to work with pharma, because it advances our singular goal: to make women’s lives better.”

Women’s Brain Foundation

Antonella Santuccione Chadha
Antonella Santuccione Chadha, Ph.D.
While working as a senior clinical reviewer at Swissmedic, Switzerland’s drug and medical device regulatory authority, Dr. Antonella Santuccione Chadha, cofounder and pro bono CEO of the nonprofit Women’s Brain Foundation, had the opportunity to help develop clinical guidelines for Alzheimer’s disease. That effort, which included regulators from Japan, Canada, Europe, and the U.S., led to the release in 2018 of FDA and EMA guidance documents for drug developers.

Work on the guidelines was eye opening for Santuccione Chadha. “That was when I started to become acquainted with sex and gender differences in drug effects and drug safety profiles,” she says. “I thought, we have to solve this problem in a systematic fashion.” The resulting Women’s Brain Project — which became the Women’s Brain Foundation in 2024 — is now working to raise $30 million to launch the Research Institute for Sex and Gender Precision Medicine.

As the first international organization focused exclusively on sex and gender differences in the context of drug development and treatment, the Research Institute will focus on four key areas: preclinical and clinical research and real world evidence; regulatory frameworks and clinical practice; research policy and advocacy; and novel technologies and AI. A coalition backing the institute and foundation will include industry scientists and experts, international research organizations and academic centers, as well as political and healthcare networks.      

Wholesale change is needed in the development of new drugs and clinical trial design, says Santuccione Chadha, who worked on the early characterization of Aduhelm (aducanumab), the first FDA approved disease-modifying drug for Alzheimer’s. She joined Biogen for the launch of Aduhelm, which ultimately failed, demonstrating the “difficulty of bringing novel drugs to patients in the field of brain and mental health.” Santuccione Chadha also has worked at Roche as a CNS and psychiatry medical manager, and as a senior medical director in Alzheimer’s disease. “We have to be more mindful about the prevalence of a condition within specific populations,” and bake that information into trial design, says Santuccione Chadha.

The Cost Of Ignoring Sex And Gender

Aside from the very real health consequences of a mismatch between clinical trial patient populations and how a drug is prescribed in the real world, a lot of revenue is at stake. Drugs withdrawn for safety reasons from commercial markets globally between 1980 and 2023 were 3.5 times more likely to be withdrawn due to women’s health risks compared to men’s health risks, according to the World Economic Forum and McKinsey Health Institute report (figure 7, page 12). Since 2000, serious or fatal adverse events have occurred in women 36% more often than in men.

Women's Brain Foundation campaign ad
Women's Brain Foundation campaign ad
The withdrawal of a drug from global markets represents a loss of 20 years of research, in addition to the drug’s revenue, notes Santuccione Chadha. Improving clinical trial design to better reflect female disease prevalence “will make things a little bit more expensive up front, but the risk mitigation will be very positive, because you won’t lose so much money,” she says. “If you avoid having a drug removed entirely from the market, you will have saved billions.”

Excluding women in trials can also make medicines unavailable to patients that need them. The fact that Gilead did not include a single cisgender woman in trials supporting the FDA approval of Descovy for HIV pre-exposure prophylaxis (PrEP) “is a crime, because they have basically lost half of the patient population,” says Santuccione Chadha. As a result of that gap in trial data, FDA excluded use in cisgender women, since “this population has not been evaluated,” according to the drug label.     

Santuccione Chadha is keen to collaborate with drug developers and biopharmaceutical companies under the auspices of the Women’s Brain Foundation. “I come from the pharmaceutical industry, I’ve worked in biotech, I’ve been in big corporations and startups. For me, transformation comes from within,” she says. “We aren’t here to tell the industry that they have done the wrong things … we want to work together with the industry to make things better.”

The full extent of sex and gender differences in medicine, from drug dosage to changes associated with aging, are only just beginning to be elucidated. How hormonal fluctuations over a lifetime — in men and women — effect the way a drug functions, for example, is still ‘not at all considered,” says Santuccione Chadha. “It’s beyond absorption, it’s beyond metabolism, it’s about pharmacodynamics, even how a compound might bind differently into the brain region of a man, versus a woman.”

Too often, women’s health is still reduced to “bikini medicine,” meaning differences in genital and reproductive anatomy, says Santuccione Chadha. Going forward, drug developers must operationalize the fact that “we have substantial differences that need to be taken into account.” Improvements in medicine for half of the world’s population is no small opportunity.