Breakthroughs Blog: Contraceptives

An estimated 257 million women globally who want to avoid pregnancy are not using safe, modern contraceptive methods, leading to around 121 million unintended pregnancies globally every year—nearly half of all pregnancies. Ensuring all who wish to use contraception have access to safe, effective, and acceptable options can enable all people of reproductive potential to enjoy greater autonomy over their lives and health. To meet the diverse needs of people of reproductive age, we need a variety of new contraceptive choices, including options that are longer-lasting, more discreet, have fewer side effects, and require fewer visits to a health care provider, as well as additional options for men to take more of the burden of pregnancy prevention off the shoulders of women. In recognition of this year’s World Contraception Day, GHTC is highlighting six technological solutions in the pipeline that could enable greater access to contraception by breaking down barriers, especially for underserved populations and those in low-resource settings. 1. Next-generation contraceptive vaginal rings   Intravaginal rings—flexible silicone rings that are self-inserted into the body and release contraceptives—offer an easy-to-use, convenient, and discreet contraceptive option for many women worldwide. Today, women can choose from either a monthly or a yearly ring—the latter of which was developed by Population Council and first approved by the US Food and Drug Administration (FDA) in 2018. However, both ring options use a combination of the same estrogen hormone, ethinyl estradiol, and different types of progestin hormones. While these hormone options work well for many individuals, for others, they can cause side effects or risks, creating a need for rings with alternative hormones and rings that are nonhormonal. Thankfully, several next-generation rings are on the horizon.These next-generation options include two rings under development by Population Council, which use alternative hormones. The first, the three-month Nestorone®/estradiol intravaginal ring uses a form of estrogen that, unlike ethinyl estradiol, is not associated with an increased risk of blood clots in the veins among women with a higher body mass index—who account for 15 percent of adult women. It is currently being evaluated for use in women with a higher body mass index in a Phase 2b study.  The second, the Nestorone®-only vaginal ring, has no estrogen, offering an alternative for those who have estrogen sensitivities, those who are at higher risk of blood clots, and postpartum breastfeeding mothers, who are often advised against using hormonal contraception that contains ethinyl estradiol due to its effect on milk production and composition. The ring will soon undergo a Phase 2 dose-finding study.On the nonhormonal front, Daré Bioscience is developing Ovaprene®, a monthly vaginal ring which uses a “semi-permeable polymer mesh barrier” to physically stop sperm from entering the cervical canal. Early clinical studies found that the ring is well-tolerated and acceptable to sexually active women and their partners. Additional clinical trial results announced in 2024 also demonstrated safety and efficacy, paving the way for a Phase 3 trial now underway.2. Biodegradable contraceptive implant  Today’s contraceptive implants are small, flexible rods inserted under the skin that continuously release hormones for pregnancy prevention. While they are safe and long-lasting, after three years, they must be removed by a medical provider. That can be an issue, particularly in low-resource settings worldwide where fewer trained health care workers, distance, and cost can serve as barriers to care. Biodegradable contraceptive implants, which dissolve into the body, offer promise as a more convenient option that could improve access by cutting out the need for a trip to a medical facility for device removal.FHI 360 and development partners pH Sciences and Gesea Biosciences, with funding from the Bill & Melinda Gates Foundation, developed a biodegradable implant called Casea S, which can provide protection against unintended pregnancy for 18 to 24 months. The implant is now being tested in a Phase 1 clinical trial, the first trial for a biodegradable contraceptive implant in more than 20 years.3. Microneedle contraceptive patches   Many women choose to use injectable forms of contraception for long-acting protection, but, for others, the need for regular shots and visits to a health care provider can make this a less desirable choice. But imagine if these injections were pain-free and did not require leaving home. That is the promise of microneedle or microarray patches, which are small Band-Aid-like patches that contain hundreds of microneedles that slowly release drugs into the body when pressed against the skin. The new technology, which is also being developed to deliver vaccines and therapeutics, could offer a discrete, user-controlled, and less painful option that could either be self-administered or administered by a health care provider with minimal training.  With support from the US Agency for International Development through the US President’s Emergency Plan for AIDS Relief, PATH is developing an easy-to-use, discreet, and self-administered contraceptive patch that could provide protection against unintended pregnancy and HIV, which is currently in preclinical development.FHI 360, in partnership with Population Council and the Georgia Institute of Technology, is also developing a three- to six-month, biodegradable, and progestin-only patch currently in the preclinical phase, with support from the US Agency for International Development and the Gates Foundation.4. Longer-acting contraceptive injectablesThe most commonly used contraceptive injection, depot-medroxyprogesterone acetate (DMPA), approved by FDA back in 1992, offers a longer-lasting option than the daily pill, with a three-month period between injections. However, DMPA requires users to return often to their health care providers, and it has the highest discontinuation rate among contraceptives in the United States due to unpleasant side effects like menstrual irregularities, weight gain, and bone density loss.FHI 360 is in the midst of a Phase 3 trial testing a six-month version of DMPA that is injected under the skin rather than into the muscle, which could offer a longer-lasting, lower-dose option that is more convenient and presents a lower risk of side effects for users. The product, which is the furthest-along six-month injectable in the pipeline, could be approved as early as 2025 or 2026 if trials prove successful.  FHI 360 is also developing a six-month self-injectable contraceptive that uses levonorgestrel rather than DMPA and is being advanced through Phase 1 clinical trials in collaboration with the Shanghai Institute for Biomedical and Pharmaceutical Technologies, with funding from the Gates Foundation. This product could offer another longer-lasting option with potentially fewer side effects and the convenience of using it at home.  5. Male contraceptivesThe need for male contraceptive options beyond condoms and vasectomy to allow men to more equally share the responsibility of contraception has been widely and increasingly recognized. There are a number of technologies in development, including technologies that use hormones to disrupt the sperm creation process. Population Council has developed a novel, easy-to-use, and reversible gel hormonal contraceptive method that is applied daily to the shoulders and, if approved, would be the first-of-its-kind option for men. Early studies showed that it is well tolerated and causes no serious adverse events. A Phase 2b study yielded promising results, with a second part of the trial now underway. The gel, which could enter the final phase of testing in 2025 with the go-ahead from FDA, has made it excitingly far in a pipeline lacking in male contraceptive technologies beyond the preclinical stage.While hormonal strategies require a long time to start and stop working because of the considerable months-long sperm development process and could have side effects due to hormone disruption, there are also nonhormonal technologies in early-stage development. These nonhormonal strategies target specific processes later in sperm development and could start and stop working more quickly, perhaps even to the point of an on-demand product taken right before intercourse. One recent study in mice identified a new nonhormonal, reversible method that targets a protein complex important during sperm production, with the drug successfully stopping the process without producing side effects or causing irreversible effects. Another recent study in mice identified a different protein target necessary for fertility, finding similarly positive results.  Contraline and Next Life Sciences are also developing nonhormonal products that work by blocking the vas deferens, the tube in the male reproductive system that transports sperm, with an injectable gel. Contraline announced positive interim results from a first-in-human trial earlier this year. 6. Dual-use technologies for HIV, STI, and pregnancy preventionMultipurpose technologies that protect against unintended pregnancy, HIV, and other sexually transmitted infections (STIs) could be a game-changer in opening up access to prevention tools, particularly in low-resource settings, by reducing the burden on users and the health care system.In addition to the aforementioned microneedle patch for HIV and unintended pregnancy prevention, Population Council is developing several dual-use products. The two products likely to reach market fastest are a dual-use pill, which reformulates already approved medicines for oral pre-exposure prophylaxis and oral contraceptives into one tablet to be taken daily, and the dapivirine-levonorgestrel vaginal ring, which builds on the successful development of the one-month dapivirine ring for HIV prevention with a three-month ring that slowly releases the antiviral drug dapivirine and the contraceptive hormone levenorgestrel, drugs already approved in other forms. Other products in early development include a nonhormonal vaginal ring and a nonhormonal fast-dissolving vaginal insert, both designed to provide crosscutting protection against unintended pregnancy and STIs.Currently, contraceptive research and development is greatly underfunded, and there is an urgent need for new and improved products to better serve particular populations and those living in low-resource settings. The contraceptive technologies detailed above and others in the pipeline offer hope that we will in the future have a robust array of contraceptive options to ensure everyone globally who wants to use contraception has access to a product that works for them.  

GHTC responded to a request for information (RFI) on House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-WA)'s recently published framework that lays out the current challenges facing the National Institutes of Health (NIH) and makes recommendations for reform with the letter below, raising concerns that some of the recommendations could limit important and lifesaving work and urging that any reforms included in legislation to be thoroughly vetted to protect that work.Dear Chair McMorris Rodgers, As members of the global health advocacy community, thank you for your interest in optimizing the National Institutes of Health (NIH) and for the opportunity to provide input on the  Reforming the National Institutes of Health Framework for Discussion.We are pleased to share thoughts below on several specific proposals. However, given the significance of NIH to the health, security, and well-being of the American people and populations across the globe, it is critical to engage in a process that permits interactive discussion with and between different parties who can shed light on the day-to-day implications of these potential changes. Through this process, we can work together to identify opportunities to strengthen NIH in support of the goals and objectives of members of Congress from both sides of the aisle.    For this reason, we are deeply concerned that changes outlined in the framework have been incorporated into the Fiscal Year 2025 House Labor, Health and Human Services, Education, and Related Agencies (LHHS) appropriations bill even before the deadline for comments on the proposal. Our concern is not that the calls for reform and increased transparency are without merit but rather that any reform included in legislation be thoroughly vetted to ensure that the important and lifesaving work of NIH is allowed to thrive.In the spirit of such a process, the following text provides specific input from the global health research community and advocates on several proposals included in the framework. The community’s apprehension centers on bifurcating the National Institute of Allergy and Infectious Diseases (NIAID); collapsing several institutes and centers, including the Fogarty International Center, into a single institute; and incorporating the Advanced Research Projects Agency for Health (ARPA-H) into an NIH institute. These actions will impose barriers, both administrative and scientific, for global health research and development that will affect NIH’s reputation as the global leader in biomedical sciences, a legacy that enhances the United States’ image on the international stage as a champion of global health innovation and a steward of global health diplomacy. NIAID is the world leader in global health research and development because its basic research expands our fundamental knowledge of antimicrobial resistance, HIV/AIDS, malaria, tuberculosis, and neglected tropical diseases. As COVID-19 variants continue to arise, the complex interactions between immunity and infectious threats have reached the public’s attention as never before. Antimicrobial resistance is another example of how the intertwined nature of infectious diseases and immunity requires constant collaboration between professionals from these fields. We are concerned that NIAID will not cleanly split in two as the LHHS report and House Committee on Energy & Commerce’s proposed framework posit. Rather, the split will disrupt the research helping us defeat the most deadly infectious disease threats—past, present, and future—at home and abroad. We are also concerned that grouping the Fogarty International Center (FIC) with topically unrelated and domestic-facing institutes into the Institute on Health Sciences Research would minimize the key role FIC plays in maintaining the United States’ global health security leadership role and advancing medical progress that benefits the American people and populations across the globe. FIC is a lesser-known but hugely consequential branch of NIH responsible for training a vast network of approximately 8,500 professionals from 132 countries in public health threat response. These trainees have gone on to hold high-ranking academic and government positions and have moved the needle on neglected and emerging infectious diseases, such as HIV/AIDS, COVID-19, Zika, and Ebola.  Rather than embedding FIC in another institute, we believe an important opportunity exists to strengthen this center to play an even more impactful role in advancing the health and security of Americans. We would welcome the opportunity to discuss options such as expanding FIC’s role to encompass strengthening clinical trial capacity and strategic partnerships in countries where capacity gaps pose risks and create tragic missed opportunities for faster medical progress. Finally, we believe that maintaining ARPA-H’s independent status is important for preserving its unique approach to high-risk, high-reward innovation as initially envisioned by Congress, which does not duplicate NIH’s critical role in basic and translational research.  The agency, authorized in 2022, has not been in place long enough to evaluate federal investment in this new model. Its efforts to reverse blindness, dramatically increase the precision of tumor removal, and overcome challenges with broad significance should be given the time they need to succeed or fail. Had Congress abandoned the Defense Advanced Research Projects Agency in its first years of operation, GPS could be a matter of science fiction, not everyday use. ARPA-H has the potential to bring new scientific thought and processes to a field marked by tradition—minimizing its role risks the United States falling behind our geopolitical rivals in health innovation during an age of rapidly evolving technologies. We believe it is in the nation’s interests to put ARPA-H’s muscle toward addressing health threats within and (currently) outside our borders. Again, Chair McMorris Rodgers, we share your commitment to strengthening NIH and believe that thoughtful, bipartisan reforms, supported by thorough discussion and vetting, are key to achieving this goal. We write to advocate for robust funding and a structural, operational, and policy infrastructure that best supports fast-paced scientific, medical, and public health progress. NIH is an asset that serves US interests and contributes in profoundly important ways to the health and well-being of all around the world. We urge that congressional efforts to optimize NIH take place on a bipartisan and bicameral basis and that only changes that have been carefully vetted through a thorough, interactive, and cross-sector process are considered. Thank you for your consideration,Alex LongUS Policy & Advocacy OfficerGlobal Health Technologies Coalition (GHTC)E: along@ghtcoalition.org 

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. In a new study, researchers from the Baylor College of Medicine and partner institutions found that a novel, nonhormonal sperm-specific approach showed promise in mice as a reversible male contraception option. The researchers identified a small molecule that would inhibit a key protein, STK33, required for fertility in both mice and human males and generated modified versions of STK33 inhibitors to make them more stable, potent, and selective, eventually testing the most effective compound they generated in mice. The researchers hope to further evaluate the inhibitor and similar compounds to determine effectiveness as a potential contraception option. There has been research into a variety of different strategies for male contraception, but there are currently no approved options for men beyond male condoms.Tens of thousands of genetically modified mosquitoes have been released in Djibouti to stop the spread of Anopheles stephensi mosquitoes that transmit malaria as part of the pilot phase of a partnership between Oxitec, the government of Djibouti, and Association Mutualis. The modified mosquitoes carry a gene that kills female offspring, the only mosquitoes that bite and transmit malaria, before they can reach maturity. If successful, the modified mosquitoes will be tested in larger field trials, and operational deployment will continue through next year, hopefully boosting malaria control efforts. This partnership is the first time that modified mosquitoes have been released in East Africa and the second time on the African continent, although similar technology has been successfully used in Brazil, the Cayman Islands, Panama, and India, with more than one million modified mosquitoes released around the world since 2019.The Administration for Strategic Preparedness and Response at the US Department of Health and Human Services is moving forward with a plan to produce 4.8 million doses of H5N1 avian flu vaccine, as the current outbreak's second human case in the United States was identified this week. The two vaccine candidates are currently in bulk form, with one of the two candidate vaccine viruses reportedly well-matched to the currently circulating strain. Health officials have identified a manufacturing line at one of its manufacturing partners for fill-and-finish, which will take a couple of months to complete. Agency officials are also coordinating with mRNA vaccine makers Pfizer and Moderna about their potential involvement in vaccine development. There are additional ongoing interagency discussions about what would trigger vaccine deployment, including a change in transmission propensity, like human-to-human or animal-to-human spread; any sign of increased illness severity; a change in the complexion of the cases, like a human infection with no tie to the affected dairy farms; or the identification of a mutation in the virus.

A new report launched at Davos, from the World Economic Forum and the McKinsey Health Institute, refocused the spotlight on women’s health back in January. The report found a stark gap in health between women and men, adding up to 75 million years of life lost annually due to poor health or early death. This health gap is incredibly costly—closing it would benefit 3.9 billion women and would boost the global economy by $1 trillion by 2040 due to reductions in early deaths and health conditions, as well as the greater capacity for women to make socioeconomic contributions.In recognition of International Women’s Day, GHTC is spotlighting technologies, both available and still in development, that could help close the gender health gap and move us toward gender equity by both addressing the leading causes of morbidity and mortality for women and girls and empowering them to take control of their health and future. 1. CAB-LA and the dapivirine ring for HIV preventionHIV remains a major global challenge, especially for women and girls, who account for more than half of the 37.7 million people living with HIV and 46 percent of new infections in 2022. While the introduction of oral pre-exposure prophylaxis (PrEP) has helped drive significant declines in HIV infections globally, challenges adhering to the regimen of daily pills, as well as issues of stigma, have limited its impact in certain populations, including adolescent girls and young women. Long-acting cabotegravir (CAB-LA), developed by ViiV Healthcare, is a HIV prevention option administered by injection once every two months. CAB-LA offers an option that for many is easier to consistently use and also more discreet to receive than daily oral PrEP, which can reduce a barrier to use for those who fear stigmatization if their HIV status is exposed.The dapivirine ring, developed by the nonprofit International Partnership for Microbicides, is a flexible silicone ring inserted in the vagina that slowly releases the antiretroviral medication dapivirine over one month to reduce the risk of HIV infection. The ring offers an alternative discreet, user-controlled prevention option for women at high risk of HIV who are unable or prefer not to use other prevention methods.2. HPV vaccine and self-sampling for cervical cancer prevention and treatmentCervical cancer is the fourth most common cancer in women globally, but 90 percent of deaths from cervical cancer and more than 80 percent of cases occur in low- and middle-income countries (LMICs). This is mostly due to lack of access to human papillomavirus (HPV) vaccination (nine out of every ten cases of cervical cancer are caused by persistent HPV infection) and cervical screening and treatment services. Ensuring girls and women have access to HPV vaccines and testing can help to address the persistently high burden of preventable HPV cases and cervical cancer deaths.As of 2023, there are six vaccines for HPV available globally, which all protect against the highest-risk types of HPV that cause the most cervical cancers. While there have been many studies demonstrating the safety and efficacy of HPV vaccines, a new study published in January of 2024, which was the first to monitor a national cohort of women over a significantly long period of time (the study looks at women born between 1988 and 1996), found zero cases of cervical cancer—reinforcing HPV vaccines as a lifesaving tool that has and will continue to be a game changer for women’s health. Regular screenings for cervical cancer are globally recommended and are crucial because cervical cancer can be cured if diagnosed and treated early on. Yet 67 percent of women between 20 and 70 have never been screened for cervical cancer (by HPV or other tests). HPV self-sampling, an approach recommended by the World Health Organization (WHO) for women 30 to 60, has been shown to be about as reliable as sampling by health care providers. Additionally, it has also been shown to nearly double use of cervical cancer screening services because it offers privacy and convenience, requires little time and effort, and reduces any embarrassment, pain, or anxiety that may be associated with sampling done by health workers. 3. Next-generation contraceptivesAn estimated 257 million people globally who want to avoid pregnancy are not using safe, modern methods of contraception, leading to unintended pregnancies and then unsafe abortions, which cause up to 13 percent of all maternal deaths. Unacceptable or unsuitable contraception options are one of the leading causes of unintended pregnancy. An estimated 40 percent of women in LMICs who use a contraceptive stop within a year because of challenges, including side effects, the burden of sticking to a daily regimen, and the time and monetary cost of having to travel, sometimes far distances, to get new prescriptions. Introduction of the daily oral birth control pill helped contribute to a major increase in contraceptive use globally over the past 50 years, but contraception technology has not seen major innovations in generations, and the field is deeply underfunded, highlighting the need for new, less burdensome contraceptive options.Lyndra Therapeutics is developing a once-monthly contraceptive pill, currently in preclinical development, that could serve as one such alternative. Researchers are also developing longer-acting injectable contraceptive products, including a six-month injectable contraceptive being advanced by FHI 360. Microarray patches are another novel contraceptive option in early-stage development—they work by releasing hormones over several months and are discreet and easy to use at home. Contraception, and specifically access to a variety of contraceptive options that fit varying needs, allows women and girls to have autonomy over their bodies and lives. There remains a gap in further research into nonhormonal contraceptive options that cause fewer uncomfortable side effects or contraceptives for men that take the burden off of women.4. AI-enabled ultrasoundsAlmost 800 women died from preventable causes related to pregnancy and childbirth every day in 2020. While there are many contributing factors, one significant challenge is lack of access to diagnostic tools like ultrasounds. Fifty percent of women in LMICs received no ultrasound scans during the course of their pregnancy. Even where ultrasounds are available, they are usually bulky, expensive, and require specializing training or knowledge to operate, forcing patients to travel to specific health care facilities to access them. New technologies like Philip’s Lumify Handheld Ultrasound, which can be connected to a mobile device, offer a more compact, portable option in emergency situations or in low-resource settings when traditional ultrasounds are not available or are not feasible. The Bill & Melinda Gates Foundation is funding Philips to accelerate the adoption of artificial intelligence (AI) algorithms that can be used with the scanner to simplify the identification of key pregnancy abnormalities, with results already showing that the AI-enabled technology helped to improve informed decision-making in the care of pregnant women in rural, underserved communities. Nimble, compact technologies like this ensure that more women have access to basic, lifesaving technologies and that women, along with their health care providers, can make informed decisions about their health and pregnancy, reducing the likelihood of death from preventable causes.5. Postpartum bleeding solutionsPostpartum hemorrhage (PPH), or excessive bleeding after childbirth, is the world’s leading cause of maternal death and can lead to lasting disability and psychological trauma, despite being preventable and treatable. Adolescent pregnancies carry a higher risk of postpartum hemorrhage because adolescent uteruses are not fully developed enough to sustain a healthy pregnancy—pregnancy complications, as well as unsafe abortions, are the leading cause of death among 15- to 19-year-old girls globally.PATH and Sinapi developed a technology, called the Ellavi uterine balloon tamponade, which builds on a low-cost solution some health care providers had been using to combat PPH called a “condom catheter,” which uses items commonly found and self-assembled in a clinic to insert a condom into the uterus and then fill it with water to exert pressure on the uterine walls and stop the flow of blood. The Ellavi device was optimized to be a high-quality, simple-to-manufacture and -use, and affordable version of the “condom catheter” that could be deployed globally to save even more lives. Another simple, inexpensive solution to PPH comes in the form of a plastic sheet with a pouch to collect and measure the volume of blood loss. This tool helps health care providers better recognize when women are in danger and take action. In one large-scale study in Africa, this sheet, when used in combination with other WHO-recommended treatment options for PPH, reduced the number of women experiencing severe bleeding by 60 percent and also reduced the number of deaths from PPH.These innovative but simple and low-cost technologies are not moneymakers, but they can greatly reduce preventable maternal deaths, particularly among adolescents, illustrating a paradox in women’s health—the gap persists because many technologies that could have a tremendous impact, particularly in LMICs, do not necessarily yield the greatest profit.While these five solutions highlighted have the potential to save lives and empower women, it is clear that closing the cavernous gender gap in health will require many more new tools and improved access to existing ones. Greater investment in R&D for conditions that specifically affect women and girls and expanded roles for women and girls to engage and lead across the R&D sector can help ensure more breakthroughs are realized in our lifetimes and that resulting tools are designed with the diverse needs of women and girls in mind.