Breakthroughs Blog: Tuberculosis

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.

A Phase 1 clinical trial testing a candidate that could become the first vaccine for leishmaniasis, a disfiguring skin disease, is set to begin soon in Kenya and Brazil, where the disease in endemic, as well as in Cincinnati, Ohio, as the disease risk grows in the United States. The Global Health Innovative Technology (GHIT) Fund is supporting the trial, which will test the safety and immune response of the candidate in healthy people. The vaccine, which was developed using CRISPR gene-editing technology to mutate the parasite that causes the disease, previously demonstrated strong results in mice and has received US Food and Drug Administration approval as an investigational new drug, which allows the product to be tested in humans. The Coalition for Epidemic Preparedness Innovations (CEPI) has announced that it is providing funding to fast-track the development of three Ebola Bundibugyo virus vaccine candidates, as the concerning outbreak of the Bundibugyo strain, for which there are no approved vaccines, continues to grow in the Democratic Republic of the Congo and Uganda. Specifically, the funding will support preclinical development and Phase 1 clinical testing of Moderna’s mRNA vaccine candidate; help accomplish a key early step in vaccine manufacturing for IAVI’s vaccine, which is based on the organization’s rVSV vaccine platform; and help the University of Oxford prepare for a Phase 1 trial of its vaccine, which is based on the same platform as its Oxford/AstraZeneca COVID-19 vaccine.  Last week, Zendal announced the launch of the international MTBVAC AVANTE consortium to accelerate clinical development and prepare regulatory and policy pathways to ensure broad and equitable access of the MTBVAC tuberculosis (TB) vaccine candidate over the next four years. The current TB vaccine is more than 100 years old and offers inconsistent protection in adults against pulmonary TB, so a new and improved vaccine that is safe and effective across diverse populations who face TB risk will be essential to ending the pandemic. With funding from the Global Health EDCTP3, the consortium of 12 European and African partners will initially support two major ongoing trials in high-TB regions in sub-Saharan Africa, one evaluating the vaccine in adolescents and adults and one comparing the candidate’s protection in newborns to the existing vaccine.  

A new US National Institutes of Health-funded study conducted in seven high tuberculosis (TB)-burden countries found that a new and improved near point-of-care TB test platform was highly accurate, effective, and scaleable. Pluslife Biotech’s MiniDock MTB test platform is battery operated, low-cost, provides results in 30 minutes, and can be used with tongue swabs in addition to sputum samples, which certain groups, including babies and people living with HIV, cannot produce. The new test is well-suited for low-resource, smaller, or more rural health clinics, which may not have access to current resource-intensive, expensive molecular testing options. The University of Oxford and the Serum Institute of India have signed a license agreement to support the development, large-scale manufacturing, and potential future commercialization of the malaria vaccine candidate R78C for use in clinical settings. R78C combines two Plasmodium falciparum blood-stage antigens, designed to target the malaria parasite at multiple points in its lifecycle, offering longer and more effective protection. This new license, which builds on a long-standing collaboration between the partners on malaria vaccine work, will initially help accelerate the candidate into clinical evaluation. The Serum Institute of India’s global manufacturing capabilities will also help ensure that resulting successful malaria vaccines can be manufactured at scale and deployed affordably to malaria-endemic countries. The Medicines for Malaria Venture (MMV) and Novartis recently announced that the World Health Organization (WHO) has prequalified Coartem® Baby, the first and only antimalarial drug developed specifically for newborns and young infants weighing between 2 and 5 kilograms. This treatment will help address a long-standing gap in malaria care for this group, who are often treated with antimalarial formulations intended for use in older children, which can increase the risk of toxicity or underdosing. The prequalification designation enables countries and global procurers to start purchasing and deploying the treatment in malaria-endemic countries; Novartis is making the treatment available on a largely nonprofit basis in malaria-endemic regions.