Breakthroughs Blog: Maternal health

It is the wish of mothers everywhere to give their babies the healthiest possible start to life. It’s a feeling I remember well as I prepared to give birth to my son Homer amid an active flu and respiratory syncytial virus (RSV) season and a global pandemic—full of hope and full of fear. The first few weeks of a baby’s life are particularly worrisome and nerve-racking for any new parent. That’s because while our little ones are quickly learning to see, grasp, and respond to our voices, it will take up to three months for parts of their still-developing immune systems to mature fully. During this time, they are particularly vulnerable to viruses and bacteria that are an everyday part of life. While my husband and I were lucky to have our son enter this world in a clean and modern hospital and to be able to mostly “bubble” ourselves off from the outside world during those early days, not every parent is so fortunate. It is a well-established reality in global health that a person’s chance of survival is heavily influenced by the circumstances of their birth—including where they are born—but this disparity is especially pronounced in neonatal health.  Each year, more than 2 million babies die in their first month of life and around 2 million more are stillborn—with 98 percent of those deaths occurring in low- and middle-income countries (LMICs). These losses reflect some of the most profound and preventable health inequities globally. The potential of maternal immunization To save more babies during their vulnerable first weeks of life, scientists are increasingly looking to harness the potential of the long-standing approach of maternal immunization in an entirely new way. Pregnant women naturally pass on protective antibodies to their developing babies during pregnancy in a process known as passive immunity. As a result, vaccinating women during pregnancy can not only protect them from dangerous diseases but can also protect their newborns during their first few weeks to months of life. Maternal immunization is not a new concept. Flu vaccines, as well as tetanus, diphtheria, and pertussis (whooping cough), or Tdap, vaccines are given to mothers worldwide as a routine part of prenatal care—I received both in my third trimester—and have proved stunningly successful. Neonatal tetanus deaths worldwide have been reduced by more than 95 percent since the late 1980s thanks, in significant part, to maternal immunization, and maternal pertussis vaccination has been shown to be 95 percent effective in preventing infant deaths from whooping coughMore nascent on the scientific front are efforts to develop vaccines designed specifically for pregnant women for the purpose of maternal immunization.  Historically, research into maternal vaccines has been limited, largely due to concerns about the ethical and safety considerations of studying and administering vaccines during pregnancy.  But thanks to interest and investments from major global health research funders like the Gates Foundation and its efforts to better characterize statistical baselines for “normal” pregnancy outcomes to meaningfully enable comparative research, a small but promising pipeline of new maternal vaccines has emerged. Harnessing maternal vaccines to combat leading causes of infant death The first-to-market new maternal vaccine was an RSV vaccine from Pfizer, which was first approved by the US Food and Drug Administration in August 2023, making it the first and, still, the only available maternal vaccine to protect infants against RSV, a common respiratory disease that claims the lives of 100,000 children under five each year, with half of those deaths occurring before six months of age. The vaccine, which is given to pregnant women between weeks 32 to 36 of pregnancy, helps protect infants during their first six months of life.More recently, the vaccine was recommended and then later prequalified last month by the World Health Organization, which should help support the procurement and uptake of the vaccine worldwide, particularly in LMICs, where the mortality burden of RSV is the greatest.Beyond RSV, maternal vaccines are being advanced against two other infections that are significant drivers of infant deaths worldwide, Group B Streptococcus (GBS) and Escherichia coli. GBS bacteria, if transmitted to an infant during pregnancy or childbirth, can lead to serious and deadly conditions, including meningitis, pneumonia, or sepsis. It’s a common infection: about one in four pregnant women carry it, but the resulting health outcomes for infants are drastically different depending on where in the world one gives birth. In high-income countries, pregnant women are screened for GBS as part of routine prenatal care, and, if infected, they are given antibiotic treatments prior to delivery. In low-income countries, with less capacitated health systems, this care is less likely to occur, leading to a stark difference in health outcomes. An estimated 97 percent of infant GBS deaths are in LMICs.But the future could look brighter. A promising maternal vaccine for GBS from Pfizer completed Phase 2 clinical trials in 2023 and received a breakthrough designation from the US Food and Drug Administration to expedite its development and review. A second vaccine candidate from MinervaX is also in Phase 2 development. Researchers estimate that maternal GBS vaccination could prevent more than 50,000 GBS-related deaths and 170,000 preterm births annually. Similar to GBS, E. coli is a common bacterium, often transmitted from mothers to their babies during childbirth, which can cause serious illnesses, including meningitis and sepsis. Proper screening and antibiotic treatment during pregnancy can greatly reduce these risks, but for those newborns that do develop sepsis, the speed with which treatment is delivered is a key determinant of survival. The risk of death from neonatal sepsis increases by 7.6 percent every hour that treatment is delayed, underscoring the risk for infants in LMICs, who are more often born outside health facilities and far from medical care.GHTC member the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator is supporting the development of GlyProVac’s maternal E. coli vaccine, which is still in the early stages of development but, if proven effective, could one day save the lives of at-risk newborns.Healthy beginnings, hopeful futuresAs a parent, I’ve experienced the fear and feeling of helplessness that often comes with having a sick infant. You snuggle and comfort their fragile bodies, doing what you can—including vaccination when available and accessible—but often, especially in low-resource settings, there is little to do beyond monitoring, waiting, and hoping they get better. I know that if the option existed to get a few additional shots to help protect my baby during those early vulnerable weeks of life, I, and so many mothers worldwide, would joyfully jump at the opportunity. In the years ahead, maternal immunization could play an even greater role in preventing hundreds of thousands of newborn and fetal deaths. By embracing its promise, we can help give babies everywhere a healthy beginning and a hopeful future. 

There is a well-known Chinese proverb that says, “Women hold up half the sky,” but when it comes to global health, sadly, humanity has a lot of ground to make up to close the stark gap between the health outcomes of women and men.While women tend to live longer than men, this longevity often comes with a greater burden of disease and disability, underscoring the urgency of addressing sex-based disparities in health care. Women, on average, spend 25 percent more of their lives in poor health compared to men, they are 52 percent more likely than men to have an adverse drug reaction and 29 percent more likely to die from one, and they’ve been found in one multi-decade study to be diagnosed later than men for more than 700 diseases. Research and development (R&D) for female-specific conditions also remains vastly underfunded: only 1 percent of R&D funding focuses on non-cancer-related women’s health.Yet despite these sobering statistics and new threats to the future of women’s health care and research funding, GHTC remains optimistic. With sustained support and investment, the scientific landscape holds immense potential to drive breakthroughs that can close these gaps and improve health outcomes for women worldwide.Thus, in recognition of International Women’s Day, GHTC is spotlighting five promising technologies in the research pipeline that could improve women’s health globally.1. A new treatment for gonorrheaGonorrhea is a sexually transmitted infection, more prevalent among women than men, that can cause serious health issues—from pelvic inflammatory disease to infertility and ectopic pregnancies—if left untreated. Combating gonorrhea has become more complicated in recent years, as growing drug resistance has reduced the arsenal of available treatment options.But, excitingly, a new, much-needed breakthrough is on the brink. A first-in-class antibiotic, zoliflodacin, developed by GHTC member the Global Antibiotic Research and Development Partnership, was found to be effective in a large-scale global Phase 3 clinical trial in 2023. If approved, it would become the first new antibiotic for treating gonorrhea in decades. The drug is also taken orally, which would simplify treatment administration for clinicians around the world, and its nonprofit developer, which is committed to delivering affordable access to the product, has the right to commercialize it in more than three-quarters of the world’s countries, including all low-income countries and most middle-income countries. Another second promising antibiotic for gonorrhea from GSK, gepotidacin, is also in late-stage development.2. A therapeutic vaccine for cervical cancerCervical cancer is the fourth most common cancer in women globally, claiming the lives of 350,000 women each year. Nine out of every ten cases of cervical cancer are caused by human papillomavirus (HPV) infection.Since the introduction of the first preventative HPV vaccine nearly two decades ago, global efforts have focused on expanding immunization coverage worldwide, as well as advancing research that has reduced vaccine schedules from multiple doses to just a single dose, easing administrative costs. Yet, despite these efforts, there remain significant gaps in immunization coverage—only 27 percent of girls worldwide received an HPV vaccine dose as of 2023—underscoring the need for additional complementary treatment and prevention tools.That’s where therapeutic cervical cancer vaccines could offer promise. What if we could administer a shot to patients who have already developed precancerous lesions due to HPV that could eliminate HPV-infected calls before those cells become cancerous? This theoretical possibility could become a reality in the future. A Phase II trial of the investigational therapeutic HPV vaccine Vvax001 reported results in January, finding that the vaccine successfully induced regression of precancerous lesions in half of all trial participants. Among patients with advanced precancerous lesions, the traditional intervention is surgery to remove the affected areas, which carries the risk of side effects and complications. An effective therapeutic vaccine could reduce the number of patients who ultimately require surgery and offer advantages as an intervention that is far easier and less costly to administer in resource-limited settings worldwide.3. Inhalable oxytocin to reduce PPHPostpartum hemorrhage (PPH), or excessive bleeding after childbirth, is the leading cause of maternal deaths worldwide. While the hormone oxytocin is often administered to women following childbirth to prevent PPH by causing the uterus to contract, oxytocin products are traditionally heat-sensitive and administered via injection or intravenously, which can make this intervention challenging to administer in certain settings around the world.To solve this issue, researchers at Monash University have developed an inhalable form of oxytocin that is formulated as a dry powder requiring no refrigeration. Prior clinical research has shown that the product is comparable in effect to injected oxytocin, and now, scientists are advancing research on the best means to administer it. In late 2023, a Phase I trial assessed administration of the product using a low-cost inhaler system called the ICOone. If this product ultimately reaches the market, it could offer a much-needed alternative that would make this lifesaving drug easier to store and administer to women in need, no matter where they live.4. Biodegradable contraceptive implantsMany women worldwide choose to use contraceptive implants as their contraceptive method. These products offer unique advantages for certain women: they are long-acting and easy to use; once inserted, there is no need for users to take or do anything on a daily, weekly, or monthly basis. But eventually, they must be removed when they are no longer effective or when users change their reproductive plans. This removal procedure requires trained health care providers, and it can create an access barrier for women worldwide who live far away from health care facilities.That’s why researchers are working to advance biodegradable implants, which would dissolve into the body over time, eliminating the need for removal. In February 2024, GHTC member FHI 360 launched a Phase 1 trial of a biodegradable implant, Casea S, which aims to prevent pregnancy for 18 to 24 months. At the time, it marked the first biodegradable contraceptive implant to undergo human trials in over 20 years. While the trial will still take a few years to complete and further research will be required, if the implant is successful, it could not only help solve health care access challenges but could also address a middle-ground need between existing implants that last years and long-acting injectables, which usually last three months. FHI 360 also has a second biodegradable contraceptive implant in its portfolio, which is in early-stage development and uses a different contraceptive hormone.5. A new drug to prevent preeclampsiaPreeclampsia is a dangerous pregnancy-related condition that affects between 2 and 10 percent of pregnancies worldwide and claims the lives of more than 70,000 mothers and 50,000 babies each year. While low-dose aspirin and calcium supplements are recommended to women who are at high risk of the condition, there is currently no medicine approved specifically to prevent preeclampsia. That could change in the coming years thanks to emerging research.A British biotech company has developed an investigational, once-daily oral drug, MZe786, to prevent preeclampsia, which is in early-stage development. In animal studies, the drug, which is a form of aspirin that also releases hydrogen sulfide, elicited an improvement in maternal and fetal outcomes compared to aspirin alone. While further confirmation of these effects in human clinical trials is needed and it could be many years before such a product potentially reaches market, in 2022, the drug was awarded a fast-track development status by the United Kingdom’s regulatory agency, becoming the first pregnancy-related drug to receive this status, signifying its potential to address an urgent and unmet need.All five of these promising products are inspiring examples of the stepwise progress achieved through past investments in women’s health research, but we also hope that they will serve as a rallying cry to what more could be possible if we were to devote adequate resources to addressing these challenges.This International Women’s Day, we hope that the global community will further commit to investing in innovations for women’s health and to expanding the representation of women in clinical research. After all, closing the women’s health gap is not only essential to the well-being and future of millions of women and girls worldwide, but it will also enrich the well-being and economic stability of their families, communities, and nations. It’s a responsibility and opportunity we can’t ignore.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A recently published study found that a malaria vaccine candidate given to women who planned on becoming pregnant was safe and effective for both the women and their babies. This exciting research could lead to a vaccine to protect pregnant individuals— who are often excluded from clinical trials—and their babies from malaria in the face of an estimated 50,000 maternal deaths and 200,000 stillbirths every year caused by malaria infections in pregnancy. The investigational attenuated vaccine, PfSPZ, will next be tested for use during pregnancy and in a larger study on preconception use. Just as the World Health Organization and the Africa Centres for Disease Control and Prevention declared the current mpox outbreak a public health emergency last week, SIGA Technologies and the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health reported mixed results from a preliminary analysis of a study testing the smallpox antiviral treatment Tpoxx against mpox. While the study, which took place in the Democratic Republic of Congo and began during the 2022 global outbreak, did not meet the trial’s primary endpoint of reducing the time to lesion resolution within a 28-day treatment period, the company says these results are not entirely unexpected and is highly encouraged that Tpoxx did elicit a “meaningful improvement” in some participants with severe cases, supporting a potential use case as post-exposure treatment for patients with severe mpox. The company also pointed to four other ongoing studies that significantly differ from the Congo trial and will provide additional data on the treatment.The NxTAG Respiratory Pathogen Panel, which detects and differentiates between common respiratory viruses, recently received 510(k) clearance from the US Food and Drug Administration. The combination test, which was developed with support from the Biomedical Advanced Research and Development Authority (BARDA) can, from a single swab, detect and differentiate 19 common respiratory viruses, including the virus that causes COVID-19, influenza A and B, and RSV, allowing health care workers to test patients and provide appropriate treatment rapidly. BARDA’s support is part of a broader effort to advance diagnostic testing platforms that can be rapidly adapted to emerging threats.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The results of a new study presented at the 2024 International AIDS Conference showed that long-acting injectable cabotegravir was safe and well tolerated as an HIV pre-exposure prophylaxis method in cisgender women before and during pregnancy. These exciting results come from an extension study of the efficacy trials among cisgender women that analyzed the outcomes of more than 300 pregnancies and infants. There has been limited data on the safety of long-acting injectable cabotegravir during pregnancy, so hopefully, these findings can fill that knowledge gap and lead to greater access to this highly effective HIV prevention option for this population, who may experience biological changes and social dynamics that can increase their likelihood of acquiring HIV during and after pregnancy.Last week, the Administration for Strategic Preparedness and Response at the US Department of Health and Human Services announced $25 million in funding to Walgreens to support a decentralized clinical trial testing COVID-19 vaccines. The study specifically aims to identify vaccine correlates of protection, or measurable immunity markers that correlate with protection against disease, using licensed or authorized COVID-19 vaccines to help assess immunity duration and streamline future clinical trials. This decentralized approach, which will include about 20 Walgreens pharmacies in urban, suburban, and rural communities, allows for a more diverse pool of study participants by bringing the study closer to where participants live. The funding comes through Project NextGen, a US government-led program to accelerate the development of next-generation COVID-19 technologies, including vaccines.  New data shows that Merck & Co.’s monoclonal antibody is safe and effective at reducing the incidence of respiratory syncytial virus (RSV)-related infections in infants. The Phase 2b/3 trial tested clesrovimab, also known as MK-1654, in healthy pre-term and full-term infants, finding that the antibody reduced the incidence of RSV-related infections over 150 days when compared to a placebo and hit key safety measures. The company announced that detailed findings will soon be presented to the scientific community and filed with global regulators. Hopefully, the antibody will eventually serve as an additional tool in the growing toolkit of new vaccines and monoclonal antibodies to address the burden of RSV in infants and older adults.