Breakthroughs Blog: Antimicrobial resistance

Last week, the Serum Institute of India announced that it will manufacture a promising tuberculosis (TB) vaccine candidate in late-stage development under an agreement with the Gates Medical Research Institute (Gates MRI). The candidate, M72/AS01E, which is currently being evaluated in a late-stage clinical trial, was originally developed by GSK before being licensed to the Gates Foundation. It could become the first TB shot in more than 100 years if approved. The agreement aims to build up manufacturing capacity to ensure adequate supply of the vaccine for rapid, widespread scale-up in key communities, if it is eventually approved. The Gates MRI will transfer the technology and know-how to the Serum Institute, which will invest more than $100 million to scale up manufacturing capacity. A Phase 1 trial evaluating a potential fast-acting, single-dose malaria treatment found promising results, as the growing threat of resistance of the malaria parasite to first-line therapies has underscored the continuous need for new antimalarials. The trial, conducted by QIMR Berghofer in collaboration with UniSC Clinical Trials and sponsored by Medicines for Malaria Venture (MMV) and GSK, found that the novel drug MMV367/GSK3772701 rapidly killed malaria parasites and was generally well tolerated in infected volunteers, appearing to work by blocking two enzymes critical to the survival of the malaria parasite in red blood cells. The treatment candidate belongs to an entirely new class of antimalarials that work differently to existing treatments, making it less susceptible to resistance. It also has the potential to be administered as a single-dose therapy in the right combination with other anti-malaria compounds.A Phase 1 trial of a Bundibugyo ebolavirus vaccine candidate launched last week, making it the first vaccine candidate to enter clinical testing in the response to the ongoing outbreak in the Democratic Republic of Congo. The Coalition for Epidemic Preparedness Innovations (CEPI)-backed candidate was developed by University of Oxford scientists and uses the same viral vector platform as the Oxford/AstraZeneca COVID-19 vaccine. Since the early days of the outbreak, CEPI, the University of Oxford, and the Serum Institute have been working together to urgently advance the development of the investigational vaccine into clinical trials. The trial will be conducted in Oxford, United Kingdom among 50 healthy adults aged 18-55 years, evaluating the candidate’s safety and immune response. There are currently no approved vaccines or treatments for the virus. 

The Drugs for Neglected Diseases initiative (DNDi) and the Serum Institute of India have announced a new licensing agreement covering clinical testing and future access for a promising treatment for dengue, a fast-growing global disease threat. There is no specific treatment for dengue and control efforts currently rely on targeting the mosquito populations that carry the virus and deploying new vaccines, which have varying effectiveness in certain populations and haven’t achieved widespread coverage. The Serum Institute developed and optimized the monoclonal antibody treatment, finding promising safety and efficacy results in preclinical and Phase 1 and 2 trials, and is currently carrying out a Phase 3 clinical trial in India. Under the agreement, DNDi will lead a Phase 3 clinical trial set to begin early next year in dengue-endemic countries, including Malaysia, Thailand, and Brazil, and, if the treatment is successfully approved, DNDi will support affordable access in low- and middle-income countries.A new study published in The Lancet Infectious Diseases demonstrated promising results for an investigational vaccine candidate for Shigella sonnei, an important step toward developing a vaccine for the disease-causing bacteria. Shigella sonnei is one of the four species of Shigella, a highly contagious bacteria that infects tens of millions of people around the world, causing diarrheal disease. There are no licensed vaccines for any of the Shigella species, two of which, including S. sonnei, are becoming increasingly resistant to first-line antibiotics. The investigational vaccine provided high-level protection, an estimated vaccine efficacy of 89 percent, in a Phase 2 trial conducted among healthy adult participants at two US sites. The next step for researchers is to optimize the dose level and evaluate the vaccine in larger trials in high-burden settings that include children, who are among the most affected by shigellosis.Last week, the South Africa Medical Research Council and the Unit of Viral Evolution and Transmission at IRCCS Ospedale San Raffaele initiated a Phase 1 clinical trial to assess the safety and pharmacokinetic profile of a promising broadly neutralizing antibody (bnAbs) for eventual use to prevent HIV acquisition by infants and young children. bnAbs, a type of naturally occurring antibody that can neutralize multiple strains of HIV, are considered a promising approach in HIV research and could potentially be utilized in a long-acting option to protect infants from HIV transmission during breastfeeding, helping close critical gaps in HIV care options and access. IAVI and partners developed the bnAb from blood samples taken from adult participants living with HIV around the world; it was selected for further development following evidence of strong potency in preclinical trials. The trial will initially enroll 26 healthy adult volunteers to collect data on dose section, administration strategies, and safety to inform the planned infant trial. 

For decades, the United States has led the world in public investment in global health research and development (R&D). Federal support enabled the development of breakthrough technologies that are saving and improving lives in the United States and around the world. US government investment in global health R&D has also generated billions in domestic economic activity, created American jobs, and laid the foundation for future discoveries that will catalyze billions more in economic benefits in the years ahead. America’s leadership in global health R&D reflects the country’s values, entrepreneurial spirit, and commitment to improving lives globally. This year, to mark America’s birthday and celebrate the nation’s extraordinary contributions to advancing lifesaving innovation, GHTC is spotlighting four game-changing global health technologies developed by US innovators with federal support.A DR-TB drug transforming the global fight against TB Tuberculosis (TB) remains the world’s deadliest infectious disease, killing 1.23 million people in 2024 alone, with growing resistance making it even more deadly and difficult to treat.  Historically, treatment for drug-resistant TB (DR-TB) required up to 20 or more pills a day over the course of 18 months or more, and patients often experienced severe side effects, such as hearing loss. Even then, nearly half of patients who were able to access treatment went uncured.Pretomanid, developed by TB Alliance, a New York-based nonprofit product development partnership, represents a major advance in DR-TB therapy. As part of a six-month, all-oral combination regimen, it has drastically reduced treatment duration, complexity, and toxicity for patients.  This innovation was made possible through funding from the US Agency for International Development and the National Institute of Allergy and Infectious Diseases and was advanced in partnership with a broad coalition of American companies, nonprofits, and universities. Since its approval, TB Alliance has strived to make pretomanid-containing regimens more affordable and accessible, improving access to high-quality DR-TB treatment in the places that need it most.A groundbreaking HIV prevention drug poised to revolutionize the fight An estimated 40.8 million people globally are living with HIV/AIDS, and 1.3 million people became newly infected in 2024. Despite decades of progress, momentum toward ending HIV as a public health threat has slowed in recent years, and major gaps remain in our arsenal of prevention tools.  Gilead Sciences, a California-based biopharmaceutical company, developed lenacapavir, a groundbreaking new HIV prevention drug that requires just two injections per year. It offers discreet, long-acting protection, making HIV prevention more accessible and easier to sustain.  Developed using evidence from National Institutes of Health-funded research, lenacapavir is now being scaled up globally through a US Department of State-led partnership, helping ensure this innovation reaches communities in need. A next-generation polio vaccine bringing us closer to eradication The first polio vaccine, introduced in the 1950s, transformed polio from a disease that caused frequent, devastating epidemics into one on the brink of global eradication. However, outbreaks of vaccine-derived poliovirus in under-immunized communities globally have posed a major challenge to vanquishing the disease for good.To address this, PATH, a Washington-based nonprofit developer, partnered with the University of California, San Francisco; the Gates Foundation; and global collaborators to develop nOPV2, a next-generation oral polio vaccine. nOPV2 retains the advantages of the original oral vaccine but has been specifically engineered to reduce the risk of vaccine-derived outbreaks. This breakthrough benefitted from critical development support from the US Centers for Disease Control and Prevention.  More than 1 billion doses of nOPV2 have been administered in countries around the world, with an expanded network of manufacturers helping ensure global access and prevent outbreaks.  First FDA-approved Ebola treatment continuing to offer hope As the current outbreak of the Bundibugyo strain of Ebola in the Democratic Republic of the Congo (DRC) reminds us, Ebola outbreaks can rapidly escalate into international health emergencies. When the 2018-2020 outbreak of Zaire ebolavirus began in the DRC—the world’s second largest Ebola outbreak—there were no approved Ebola treatments. Inmazeb®, a novel antiviral medicine developed by Massachusetts-based Regeneron in collaboration with the Biomedical Advanced Research and Development Authority, was evaluated in a National Institutes of Health-supported trial during the outbreak. The strong results from that trial supported approval by the US Food and Drug Administration (FDA) in 2020, making Inmazeb the first FDA-approved treatment for Ebola, which has since been deployed in Ebola outbreaks in the DRC and Guinea. The most potent antibody in Inmazeb has now been recommended for priority evaluation during the current outbreak after demonstrating broad activity against multiple Ebola strains, including Bundibugyo, for which no approved therapeutics exist—highlighting how US-backed innovation continues to pay off and why sustained investment is needed to stay ahead of future threats.  Ensuring continued US leadership through sustained investment From transforming DR-TB treatment and HIV prevention to accelerating polio eradication and delivering the first Ebola therapy, the United States has long been at the forefront of global health innovation. These successes reflect the best of America: leadership, ingenuity, compassion, and a commitment to improving lives. Sustaining this impact will require continued investment and support in the programs, partnerships, and people that make such breakthroughs possible.

An international clinical trial led by the Global Antibiotic Research and Development Partnership (GARDP) seeking improved antibiotic treatments for newborn sepsis has expanded to India. Neonatal sepsis is one of the leading causes of newborn deaths worldwide and is becoming harder to treat due to rising antibiotic drug resistance. Newborns have long been underrepresented in antibiotic research, leaving health care providers without an evidence-based standard-of-care treatment. The lack of a standard treatment has in turn complicated neonatal sepsis research because there is no obvious treatment to use as a comparison in trials. The trial aims to test and rank multiple potential antibiotic combinations for neonatal sepsis.Last week, the World Health Organization announced that a clinical trial evaluating two potential antiviral therapeutics for the Bundibugyo strain of Ebola will be launched in the Democratic Republic of the Congo next week amid the ongoing outbreak. There are currently no approved vaccines or therapeutics for the Bundibugyo strain, which is only known to have caused three outbreaks in history. The trial will evaluate the ability of Mapp Biopharmaceutical’s MBP134 and Gilead Sciences’ remdesivir to reduce mortality in patients, alone and in combination. The United States and Gilead Sciences are donating all the doses that will be used in the trial.The US Food and Drug Administration (FDA) has approved the first generic version of rifapentine as part of combination treatment regimens for active and latent pulmonary tuberculosis (TB). Rifapentine was first approved by FDA in 1998 to treat pulmonary TB. For active pulmonary TB cases in patients 12 or older, the generic antibiotic is approved only in combination with one or more anti-TB drugs, while for latent TB cases, the generic is approved in combination with isoniazid to treat patients 2 or older at high risk of progressing to TB disease.