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GHTC Executive Director Dr. Kristie Mikus issued the following statement in response to the release by the World Health Organization (WHO) of new guidance on best practices in clinical trials. This guidance comes following a two-year development effort prompted by the 2022 adoption of a World Health Assembly resolution on strengthening clinical trial capacity. GHTC has been engaged in robust consultations with the WHO Science Division throughout the process.“Clinical trials are the backbone of medical progress, helping translate promising discoveries from a lab into proven solutions for the patients and communities who need them worldwide. We welcome the release by WHO of new clinical trial guidance, which will support countries, industry, and researchers in conducting better, more inclusive clinical trials during both ordinary times and health emergencies. We particularly applaud the guidance’s focus on strengthening trial infrastructure in low-resource settings and expanding the inclusion of groups traditionally underrepresented in clinical research, including children and pregnant and lactating women and individuals.  Every region should have the capacity to conduct high-quality research, and every person deserves to benefit from the fruits of science. Today’s release of WHO clinical trial guidance is a step forward in realizing that vision.” 

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.  

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 Biomedical Advanced Research and Development Authority (BARDA) has awarded an agreement worth up to $268 million over 12 years to Swiss company Basilea Pharmaceutica to support the development of novel, first-in-class antifungals and antibacterials in its portfolio. The initial funding will specifically serve the further development of fosmanogepix, which is expected to enter soon a Phase 3 trial for invasive yeast infections, and BAL2062, which has the potential to target the common mold Aspergillus and has most recently completed a Phase 1 safety study. The news comes as investment in new antimicrobials continues to wane and the threat of antimicrobial resistance continues to rise globally.A recent study found that the protection offered by the Jynneos mpox vaccine greatly wanes 6 to 12 months after vaccination, raising concerns about the need for booster doses and the potential of breakthrough infections among vaccinated people amid the ongoing global mpox emergency fueled by the severe clade 1b of the virus. The Jynneos vaccine is meant to be given as two doses a month apart, but to offer protection to more people and to conserve a limited supply of doses, many were offered just one dose early on in the 2022 clade 2 mpox outbreak. The study found that after one year, the antibody levels in participants who had two doses were comparable or lower than the peak antibody responses in people who had received only one.The US National Institutes of Health (NIH) recently announced a new network that will research pathogens that currently lack effective treatments and vaccines to identify strategies to develop safe and effective medical countermeasures before a new pandemic threat arises. The network, which comes in the wake of the COVID-19 pandemic and the midst of ongoing emerging infectious disease outbreaks, will focus on developing tools that target viral families that are known to cause human disease, such as the families that include dengue and yellow fever, measles, polio, and chikungunya. The agency’s National Institute of Allergy and Infectious Diseases has committed up to $100 million annually to the network.

It has been nearly eight years since antimicrobial resistance (AMR) gained political attention at the highest levels. At the United Nations (UN) High-Level Meeting (HLM) on AMR in 2016, countries vowed to take a coordinated approach to address the root causes of AMR. Now, close to a decade later, progress has been uneven at best. While many countries have tried to tackle the issue by developing their own national action plans, fewer than a fifth of these plans are funded or implemented. And while annual global funding for antibiotic research and development (R&D) increased by 25 percent since 2017, access remains a challenge, as many new antibiotics never get registered and remain unaffordable in low- and middle-income countries (LMICs).On September 26, the UN is hosting a second HLM, aimed at accelerating multisectoral global, regional, and national action to address AMR. Will this be the moment where key global decision-makers generate lasting political momentum to make meaningful progress addressing this silent pandemic?Renewed sense of urgency to address AMR and invest in R&DThe upcoming meeting will occur amid a sense of renewed urgency around addressing AMR. A recent Lancet report highlights that drug-resistant pathogens could cause more than 39 million deaths over the next 25 years, forecasting that AMR deaths will increase steadily in the coming decades if remediation measures are not in place.A study by the Global Research on Antimicrobial Resistance Project predicts that AMR mortality will increase by 70 percent by 2050 and notes that the most impactful way to prevent this outcome is through improving access to effective antibiotics, particularly in LMICs, where the burden of disease continues to be the greatest. The study also suggests that the traditional model of drug development may not be sustainable for antibiotics, as most new products never reach key populations in LMICs because they are not able to overcome regulatory challenges and remain too expensive. Unless access and affordability are assured, the global mortality burden from resistant bacterial infections will continue unabated. Ensuring there are political commitments to strengthen the AMR R&D ecosystem will be crucial in realizing progress.2024: The year of AMR?The good news is that, in many ways, 2024 has already been the year of AMR. In May, the World Health Organization (WHO) delegates approved a resolution to accelerate national and global responses on AMR, with many of them highlighting it as a crucial building block for the HLM this fall.The resolution welcomes WHO’s strategic and operational priorities to address drug-resistant bacterial infections in the human health sector, including strengthening R&D to support the creation of new tools to combat AMR and replenish the shockingly waning pipeline.AMR has also continued to feature in G7 and G20 discussions, and member states are largely expected to include provisions focused on combating the silent pandemic in political outcome documents later this fall, including recognizing the need for new investments in research and greater support to initiatives like the Global AMR R&D Hub.Political declaration: Commitments on a path forwardSo, what constitutes success for the HLM on AMR? Much of it comes down to the commitments and pledges made in the political declaration that will be adopted by delegates. The good news is that the final draft includes some strong targets, including one to reduce global deaths from bacterial AMR by ten percent by 2030. Countries are also pledging to develop their national action plans by 2030, of which 60 percent would need to be adequately funded by the deadline (compared to the roughly 20 percent which are to date).Perhaps most notable though is the request for the Quadripartite—which is comprised of WHO, the World Organization for Animal Health, the UN Food and Agriculture Organization, and the UN Environment Programme—to establish an Independent Panel on Evidence for Action. The panel would serve a key function by supporting member states’ decision-making with regular guidance on the trends of science, data, and evidence across AMR-related sectors.R&D is also a central pillar in the declaration, with member states recognizing the need for increased public-health-driven R&D and the role of public-private partnerships like the Global Antibiotic Research & Development Partnership and the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator. The text encourages the use of push and pull incentives to spur R&D while ensuring mechanisms are in place for equitable access. Countries are called upon to develop and incentivize the adoption of manufacturing standards, promote the transfer of technology and know-how, encourage research, and undertake measures to address the growing shortage of researchers and medical specialists.It is worth celebrating the inclusion of several numeric targets, as many past political outcome documents coming out of UN health-focused high-level meetings did not feature such specific and explicit provisions and pledges. However, while the political declaration offers a good framework for making bigger shifts in the fight against the silent pandemic and ensuring a more explicit focus on equitable access to health technologies to fight AMR, additional funding and research targets would have led to an even stronger outcome, as targets lead to better transparency and accountability.What’s next?Member states are largely expected to adopt the political declaration on Thursday without much controversy. The question is: what’s next? There will certainly be opportunities to further advance the work on AMR in other forums, such as the G7 and G20, as well as at the AMR ministerial in Saudi Arabia in November. The AMR political declaration includes a commitment by countries to raise $100 million to aid implementation of national action plans, and follow-through on the principles and targets will be key in the months (and years) ahead, especially with the next AMR meeting not scheduled until 2029. The 79th UN General Assembly will be a pivotal moment to garner the high-level political commitment needed to ensure sustained focus on the ongoing challenges around AMR and to shift from dialogue to action to combat the silent pandemic.