Women’s Health Meets Drug Design and Medical Research

Are you Swiss and planning to move abroad? Or have you already taken the leap? I'm really excited to tell you that Swissinfo has a new podcast coming out just for you. You can listen and watch it from the 25th of November. It's called Ade Mercy Shweitz and is available in Swiss German and French. It covers everything you need to know about setting up your new life abroad. We speak to Swiss around the world who've already made the move, and we ask experts to share their experiences. You'll find Ade Mercy Shweitz, wherever you get your podcasts or in our sweet plus app. Hello, I'm Jo Fey and this is a Swissinfo podcast. Swissinfo is the multilingual and international public media company of Switzerland. Welcome to the Swiss Connection Science podcast. We're currently exploring some of the biggest issues in the pharmaceutical and healthcare field. In this episode, we'll talk about the role of sex and gender in drug development. Women have always taken medicine, of course, but very rarely has this medicine been developed with women's bodies in mind, and this has had serious consequences for women's health. There's a movement to change this in many countries, including Switzerland, but there's also a lot of resistance. Our healthcare journalist Jessica Davis-plus, investigated why sex and gender have been ignored in drug development, and why this is so hard to change. This is a very timely topic. In early 2025, US President Trump issued several executive orders, meant to discourage more diversity and inclusion in medical research. Many of his decisions are still being discussed in the courts, but it shows the range of views and how contentious the topic is. On our last episode, we talked about a drug called Lycanumup, sold under the name Lecambi. That's actually where our story begins today. In July 2023, Lecambi became the first drug in 20 years to be fully approved by the United States' Food and Drug Administration for Alzheimer's Disease. The drug, which was developed by US from biogen and Japanese from azide, works by reducing amyloid plaques that form in the brain, a defining feature of the memory-robbing illness that affects some 55 million people globally. The pivotal approval of the drug showed that it slowed cognitive decline by 27% compared to a placebo, but there was a more complex story beneath the surface. There were also differences among the 1,700 patients in the study, some 51.7% of whom were women. The drug slowed cognitive decline by only 12% in women compared to 43% in men. This drug was shown to have but also other drug of the similar mode of action, seems to have a lower effect in the female population. That's Antonella Santuchoni Shada. She is a neuroscientist and the founder of the Women's Brain Foundation. Her work is focused on integrating sex and gender more fully into medicine. What it means, we don't know what it means, for the reason it just pointed. We know that cognitive decline in women and men differ, for instance, in progression. Women decline twice faster than men do. You know that the position of biomarkers at baseline differ between men and women, so one reason could be that while women have symptoms that look alike, maybe the brain pathology is more, and so the drug might not be so efficient because it should have been prescribed earlier or simpler to a higher dose. We just don't know. Santuchoni Shada argues that she doesn't think the differences are a reason not to approve the drug, but the data confirms that differences exist and that more investigation is needed. I think they did the right thing, because after the is an authority that has to decide benefit, risk profile of the drug. So, and the balance of prescribing it versus the risk, it's apparently the same for both men and women. So there isn't a higher risk or the real proof that it does not work on women. So the approval is correct. Okay, I think that the mean we have is to make post-approval studies to really understand what is going on, to make better design up front of clinical trials, to see whether women need a higher dose, maybe the administration rule must be different, maybe the time to prescribe the drug should be different. These are questions, medicine regulators and major health funders are increasingly asking themselves. Last year, the Swiss National Science Foundation, the largest public funder of biomedical research in the country, announced a national program with a budget of 11 million francs to find ways to integrate sex and gender identity into health research and medicine. The move reflects a shift taking place elsewhere at regulatory bodies, in universities, and in pharma companies. It's an attempt to overhaul the male-dominated approach to medical research and develop drug with women in mind. This isn't just about what we've traditionally viewed as women's health, meaning health that affects women's sexual organs. This is about health more generally. The list goes on. Women are more likely to have a stroke, cardiovascular disease, and autoimmune disorders such as lupus. Although women make up 70% of chronic pain patients, 80% of pain studies are conducted only on men or male mice, men still dominate many clinical trials for diseases that disproportionately affect women. The fact that more than half the participants in the main laquem be trial were women, and the study reported gender-desigrated data at all is a sign of progress. Rarely, our study results broken down by sex and gender and reported publicly. When they are, differences in the efficacy and safety for men and women are rarely considered in the approval and prescribing information for drugs. This has had serious consequences for women's health. In the past 40 years, medical products are three and a half times more likely to be removed from the market because of adverse effects on women. That's according to a McKinsey Health Institute study. In Switzerland, a recent report found that women receive treatments that aren't adapted to them. This leads to more side effects and poorer prognosis. A lot of this goes back to basic research. Male mice have been the default. Until recently, researchers saw women's bodies as smaller versions of their male counterparts. There are still five and a half times more studies using only male animals than studies that include female animals. This is just the beginning because the real problem resides in pre-clinical science. Yesterday, I had a conversation with a start-up that it's developing ABBA-ergic neurotransmitters for schizophrenia, for example, and other indications in Sweden, so Europe. The guy goes and says, "Oh, you know, I've never thought about considering, in my experiments, in my models, this sex and gender differences, and we use mainly male mice." So this problem starts already with the mouse model, that if it is not tailored or attuned, or the cell system, the organoid, the in vitro culture, if we don't consider this really upfront, I think we have already a bias that it's carried along till the phase three. Okay, thank you. Kahol Claire is a medical doctor and researcher. She heads the Health and Gender Unit at the University Center for General Medicine and Public Health. It's called Unisante in Lozan. She says there are several reasons why men have dominated medical research. One is historical, meaning this is just how research has always been done, but there are also a lot of misperceptions about sex and gender differences. I think, yes, basic research, you see a lot of research that is done on male animals also, just because people are used to it, and they don't really think about, okay, maybe maybe make a difference if I study this pain mechanism in male mice. And actually, when you do, you see differences, and then that's when you have very interesting discoveries. And that's also one aspect that men use in men are less complex, and I think it's wrong because they also have hormonal fluctuations. So men can also, male can also be complex, so I think it's interesting. The bias in the pre-clinical stage carries over into clinical trials. If we take the example of HIV, most studies on HIV have been done on male participants or maybe transgender women, but very few on cisgender women, and when you look globally, more women have HIV than men. So still today, there has been a very recent study published in New England Journal of Medicine with a prep that has been done in a sample exclusively of women, which is, I think, very interesting, but still like five years ago, we still had those large trials, large studies done mainly on men. But she adds that there are also cases where studies only recruit women. With, for example, mental health, we have more research that has been done on women, but I think men also suffer from mental health problems, probably it's underrecognized. And if we continue to do most research on anti-depressive drugs on women, probably we will never discover also the male specificities. So for me, I always said, okay, gender is not only women, it's also men. She also said there's been an assumption that a hypothesis holds true regardless of someone's sex, but studies show this isn't true. In 2022, research on the anti-aging benefits of the generic drug rapamycin in fruit flies found it only prolonged the lifespan of females and not of males. Some clues as to why are in the waste disposal process in the females intestinal cells. This differs from that of males. There are also differences in the way men and women adhere to medicine, depending in part on gender norms and roles. Claire experienced this firsthand in a study she led on cardiovascular disease. We did a study on the management and outcomes of patients who are admitted to hospital with a cardiovascular disease with a coronary heart syndrome, so it's heart, in fact, basically. We used all data from all hospitals in Switzerland. It was pretty recent. It was very simple. These were all patients that were admitted to the hospital, so they already had the diagnosis. And we were just interested in looking at their management, how the difference between men and women and their outcomes. I really did not expect this, but what we observed is that women were less likely to get the treatments that are recommended to have their creatinous coronary interventions. I have the French word, but it's coronarography. They are less likely than men to have this. They are also less likely to have bypass grafts, so they get less treatment that should be given. And when we look at their outcomes, women also were more likely to die during their hospitalization. And that was something that was really surprising because it was especially younger women, so women younger than 60 years old, that were a higher risk of dying during their hospitalization. And for me, to see these results in Switzerland today was kind of, okay, we have a problem. So for me, this is one study that's, okay, does not give solutions, but say, okay, we have a problem here still today. And then we need to really look at what's wrong. Over the last decade, authorities and regulators have started to address some of the gaps in drug research and development. In 1993, the FDA issued a guideline making clear that women should be included in all phases of clinical drug development. This reversed a previous policy banning women in child bearing years from participating in early trials. This came after birth defects emerge from exposure to some new drugs. Pregnant women are still excluded from most trials. In the same year, the National Institutes of Health in the US, which is the largest public funder of biomedical research required women to be included in publicly funded phase three clinical trials. This is when drugs are tested in large populations. Since 2014, the European clinical trials regulation has required clinical trials to represent the likely user population, including different gender groups. In 2022, the European Research Council made gender equality plans a criteria for funding. Experts I spoke with said Switzerland is slowly catching up. I think in Switzerland, we still are bit beyond other countries because it's still nuts mandatory. For example, when you submit a proposal for the Swiss National Science Foundation, it's nuts mandatory that you include men and women so you could do a trial on cardiovascular disease and include only men. Switzerland recently updated its clinical trial regulation to require inclusion of diverse gender groups. This went into effect in November 2024. The Swiss government has also tasked the Swiss Medicines Regulator, Swiss Medic, to find ways to integrate sex and gender better into its evaluation of new medicine, with changes expected by 2029. Claire is also involved in a Swiss National Science Foundation program I mentioned earlier that should also reveal ways to bridge the gender gap in early research. And Switzerland has its first full professor in gender medicine, Caroline Lechemüle at the University of Zurich. I was nominated a professor with this specific dimension of gender that was first also in Switzerland. And now in Zurich, they have a new professor in gender medicine that came this year. So I think it's developing in Switzerland. But progress around the world has been hitting roadblocks as I mentioned at the start of the podcast. On January 21st, US President Donald Trump issued an executive order on what he called ending illegal discrimination and restoring merit-based opportunity. This included a call to encourage the private sector to end what he sees as illegal diversity, equity, and inclusion, discrimination, and preferences. President Trump has attacked diversity as woke culture that he claims leads to unfair treatment. This led many websites like the Center for Disease Control and Prevention and the FDA to backtrack on some gender goals and projects. Swiss pharmaceutical companies Roche and Novartis also announced in March they were adjusting their goals on diversity and inclusion, although they have said they remain committed to some of its principles, including the design of studies to reflect the broader patient population. Claire said that talking about gender has always faced resistance. I kind of began very carefully with always this difficulty when you talk about gender that people say either they think oh yes we need more women or we're inductors more for researchers. So that's one aspect but that's not what I was interested in. All they think you are felonists and you want to do some revolution. Yes, revolution and it's not scientific. Sent to join each other and Claire agreed this isn't politics, it's really just good science that would benefit everyone. I always say six gender analysis is not rocket science, it's common sense. It's such an interesting topic Jessica and I'm really wondering now after hearing everything that we've gone through in this episode, if you think that this field will be able to overcome the many growing hurdles that are facing it from really a global perspective. I do to some extent I think a lot of scientists and companies have realized that they can produce better medicine and maybe even understand diseases better if they investigate sex and gender. Okay Jessica thank you very much for bringing us this story. Thank you. Coming up next time on the Swiss Connection Science podcast we'll find out how AI is helping develop new medicine. For more science stories visit our websites for sinfo.ch and you can help other people to find our podcast by leaving us a five-star review wherever you get our podcast. Today's episode was recorded and edited by our science and video journalist Michaela Andina. For more content visit our website Swissinfo.ch. I'm Jo Fey. Thanks for listening.