Hannah Sachs-Wetstone

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. Last week, scientists in Rwanda and partners from the World Health Organization launched the world’s first clinical trial testing a treatment for the deadly Marburg virus amid the ongoing outbreak in the country. There are currently no approved treatments or vaccines against Marburg virus, although a clinical trial of Sabin Vaccine Institute’s investigational vaccine is currently underway in Rwanda. The new trial will investigate the safety and efficacy of remdesivir and the monoclonal antibody MBP091, developed by Mapp Biopharmaceutical with support from the Biomedical Advanced Research and Development Authority.  At the recent G7 Joint Finance and Health Ministers’ Meeting, the Italian government announced a $21 million commitment over the next three years to the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to accelerate the development of innovative products to prevent, diagnose, and treat drug-resistant bacterial infections. AMR is a growing public health crisis, particularly in low- and middle-income countries, and there is an urgent need for international collaboration and investment to revitalize an inadequate clinical pipeline and ensure new antimicrobials, antimicrobial alternatives, and diagnostics are available for patients worldwide.Valneva and LimmaTech announced last week that their Shigella4V (S4V) vaccine has been awarded Fast Track designation by the US Food and Drug Administration. There are no approved vaccines for the Shigella bacteria, which causes shigellosis, the second leading cause of fatal diarrheal disease globally, particularly among children in low- and middle-income countries. S4V is the world’s most clinically advanced tetravalent bioconjugate vaccine for shigellosis. This designation will enable accelerated clinical development and review of the vaccine, which will be investigated in two Phase 2 trials that are expected to begin before the end of 2024.

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. Recently published results from a Phase 3 clinical trial support Pfizer and Abbvie’s aztreonam-avibactam as a potential treatment for patients with serious gram-negative bacterial infections and limited treatment options. Aztreonam-avibactam is a combination of two antibiotic drugs that work together to effectively fight off tricky bacteria resistant to nearly all currently available antibiotics. The treatment was approved in April by the European Medicines Agency based on the results of two previous Phase 3 clinical trials that investigated the treatment's efficacy in treating several types of multidrug-resistant infections.Last week, TB Alliance announced the award of a $7.35 million four-year grant from the US Department of Defense’s Congressionally Directed Medical Research Programs for the research and development of host-directed approaches for treating tuberculosis (TB). Host-directed approaches, which target the immune response of the host (the infected person) rather than directly targeting the bacteria, could reduce the likelihood of the emergence of drug resistance and, in combination with new TB drugs, could offer shorter and less long and burdensome treatment regimens for those with drug-resistance and drug-sensitive TB. Specifically, the project will work toward preclinical proof-of-concept for at least one novel adjunct TB host-directed therapy and one therapeutic vaccine.At the HIV Research for Prevention Conference last week, the Population Council announced the results of a Phase 1 trial conducted in South Africa, which suggest that the three-month dapivirine vaginal ring for HIV prevention will be as effective as the one-month ring. The three-month dapivirine vaginal ring, a flexible silicon ring self-inserted into the vagina that slowly releases an antiretroviral drug to prevent HIV infection, was found to deliver the drug at higher levels than the one-month ring. If the longer-acting ring continues to demonstrate success in future trials, it could offer a more cost-effective and convenient option for women—it is expected to reduce the cost per user by 60 percent.  

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. Amid the ongoing outbreak in Rwanda of the deadly Marburg virus, Rwandan health authorities announced Sunday that they will begin a clinical trial of a vaccine against the virus, for which there are no approved therapies or vaccines. The trial, which will deploy an investigational vaccine from the Sabin Vaccine Institute, will target health workers, emergency responders, and individuals who have been in contact with confirmed cases, according to the Health Ministry. The Rwanda Biomedical Centre will serve as the trial sponsor.Last Wednesday, Gilead Sciences announced a plan to allow six generic pharmaceutical companies in India, Pakistan, and Egypt to produce and sell the twice-yearly HIV prevention injectable drug lenacapavir in 120 countries, including all those with the highest HIV rates globally. This news comes after results published earlier this year from two clinical trials showed that the drug was extremely effective at preventing HIV across key populations—cisgender women, gay men, and trans and nonbinary people, who were all represented in the trials. While the new plan aims to enable rapid and broad access to the drug in many countries, the deal excludes most middle- and high-income countries, which account for around 20 percent of new infections. In those countries, the originator drug will only be available at higher prices, making it potentially unaffordable and inaccessible to at-risk populations, particularly those in middle-income countries.Last week, the World Health Organization (WHO) issued new recommendations encouraging vaccination of pregnant women and administration of antibody shots to newborn babies to protect against respiratory syncytial virus (RSV), which is a leading cause of severe infection and death in babies, with a majority of RSV-related deaths occurring in low- and middle-income countries. There is only one vaccine, Abrysvo, for pregnant women and one antibody shot, Beyfortus, for infants and toddlers available in the United States and a handful of other countries. Supply of these products is limited and the cost, specifically of Beyfortus, is high, which could limit global access and affordability until lower-cost, more widely available existing products and new, innovative products enter the market.

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. Two recent studies found that the virus that causes COVID-19 is developing resistance to two antiviral drugs commonly used for treatment in patients with compromised immune systems: remdesivir and nirmatrelvir. The first study from Cornell University and US National Institutes of Health researchers, which specifically looked at immunocompromised patients, found that the virus developed a reduced sensitivity to the drugs, while the second study from University of Pittsburgh, Brigham and Women’s Hospital, Stanford University, and Harvard University researchers also found resistant mutations, with the effect more evident in the immunocompromised and those who had received nirmatrelvir. These results raise concerns as the threat of antimicrobial resistance globally grows.Researchers from the University of California, Riverside; the University of California, Irvine; and the Yale School of Medicine have designed a new synthetic compound, MED6-189, which is effective against drug-sensitive and drug-resistant Plasmodium falciparum malaria strains in vitro and in mice engineered to have human blood. MED6-189, inspired by a compound extracted from marine sponges, works by targeting and disrupting a specialized part of P. falciparum cells, as well as the pathways used to transport materials within the cells, thereby preventing the pathogen from developing resistance. The next steps include continued optimization of the MED6-189 and further confirmation of its mechanisms of action, but, if the compound continues to demonstrate success, this research could lead to the development of an important tool to address the rising challenge of antimalarial drug resistance.Last week, the US Department of Health and Human Services through the Advanced Research Projects Agency for Health announced funding for the Transforming Antibiotic R&D with Generative AI to stop Emerging Threats project that will use artificial intelligence (AI) to speed up the discovery and development of new classes of antibiotics to meet the urgent need for new drugs amid the growing threat of antibiotic resistance. While conventional antibiotic discovery methods require time-consuming manual screening and testing of potential molecular compounds, most of which do not advance into further development, this project will employ deep learning to develop new methods to identify biomolecules with potential and use generative AI to expand the number of potential antibiotic candidates.

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.