Breakthroughs Blog: Pandemic preparedness

The Democratic Republic of the Congo has approved the use of a new single-dose oral treatment for sleeping sickness, a potentially fatal disease which is endemic in several countries in Central and West Africa. The approval of Acoziborole Winthrop, codeveloped by the Drugs for Neglected Diseases initiative (DNDi) and Sanofi, follows successful Phase 2 and 3 clinical trials conducted in the DRC and Guinea by DNDi in partnership with national authorities, which demonstrated that the drug is safe and effective. Existing treatments require a ten-day oral treatment regimen or a combination of injection and oral therapy that requires several days of hospitalization for patients in the most advanced stages. The DRC approval, which will make the drug available free of cost to patients in the country, is expected to be followed by endorsements in other endemic countries soon.A research team from the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health has shared promising early results from a first-in-human clinical trial comparing a new investigational vaccine against Lassa fever and rabies to a licensed rabies vaccine, finding that the vaccine candidate was safe and induced rapid and robust immune responses against both viruses. There are currently no available vaccines for Lassa fever, a dangerous disease considered a priority threat with epidemic and pandemic potential that is common in parts of Western and sub-Saharan Africa, which also have a high burden of another severe disease: rabies. A dual vaccine could help streamline health care delivery in settings with limited health care infrastructure; the vaccine candidate can also be freeze-dried for storage, making it well suited to low-resource settings where it can be difficult to maintain the cold chain. Last week, DNDi, the Medicines for Malaria Venture (MMV), and the Global Antibiotic Research and Development Partnership (GARDP) announced a new cooperative agreement to explore how the three organizations can work together to advance global health research and development (R&D) amid global aid cuts and calls to reshape the global health architecture. The organizations plan to pool their expertise and resources to advance the R&D of effective and affordable medicines, while centering patient needs and equity. In addition, the partners will collaborate on policy advocacy and communications activities to raise awareness of the impact and promise of the nonprofit product development partnership model in advancing innovative, lifesaving medicines for critical, but often overlooked, diseases.  

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.  

Amid the ongoing outbreak of the Bundibugyo strain of Ebola—for which there are no specific approved vaccines or therapies—in the Democratic Republic of the Congo and Uganda, the World Health Organization (WHO) has collaborated with outside experts to identify priority Ebola treatments and vaccines for clinical trials. On the treatment side, WHO recommended prioritizing Mapp Biopharmaceutical’s MBP134, Regeneron’s maftivimab, and Gilead Sciences’ antiviral remdesivir. For prevention, Gilead's experimental oral antiviral obeldesivir was highlighted as a priority for post-exposure use in contacts of confirmed cases. IAVI’s rVSV Bundibugyo was identified as the most promising vaccine candidate, but Oxford University and the Serum Institute of India’s ChAdOx1 Bundibugyo vaccine candidate could be available for testing sooner following additional animal testing. WHO is now working with authorities in Congo and Uganda and other partners to design and implement ethical clinical trials during the outbreak. An experimental drug for chronic hepatitis B could potentially serve as a functional cure for the virus, as demonstrated in recently published results from two international studies. For many, hepatitis B only causes short-term illness, but for some, it can become a chronic infection, gradually damaging the liver and, without treatment, leading to liver cancer, liver failure, or even death—it causes around 1.1 million deaths globally each year. Chronic infection requires lifelong therapy in the form of daily pills to reduce viral levels and prevent liver damage, which can be hard to adhere to or access in some countries. Bepirovirsen, developed by GSK and Ionis Pharmaceuticals, was able to reduce the virus in around one in five patients to levels low enough for the immune system to keep it under control without treatment. The drug is under fast-track review by the US Food and Drug Administration, which is expected to make a decision later this year, and is also being considered by international regulators in Japan, China, and Europe. A research team at Georgia State University has developed a promising antiviral drug candidate that could help treat measles, croup, and related viral diseases that cause contagious and life-threatening respiratory infections, as falling coverage of the vaccine for measles, mumps, and rubella raises the risk of infection. The drug, GHP-88310, was designed to be a once-a-day oral pill for vulnerable patent groups, like children and immunocompromised patients, which make up the majority of croup and measles cases. GHP-88310 has been shown to be well-tolerated in rats, mice, ferrets, and dogs at higher concentrations. 

Last week, the Global Health Investment Corporation announced the launch of the Global Health Security Fund, which will strategically invest in companies to accelerate the development of technologies that strengthen global health security. The investments will focus on companies developing vaccines, therapeutics, diagnostics, and enabling technologies with impact and commercial potential, addressing critical gaps in global health preparedness and response. The fund has received support from the US Biomedical Advanced Research and Development Authority (BARDA), as well as investors including the Coalition for Epidemic Preparedness Innovations (CEPI), Flu Lab, Eli Lilly and Company, Meiji Seika Pharma Co., The MITRE Corporation, and the Wisconsin Alumni Research Foundation. A research team at the La Jolla Institute for Immunology has shared promising research that could inform the development of a vaccine that provides protection against a host of viruses in the arenavirus family. Arenaviruses, which are most common in West Africa, are considered to be a viral family with significant pandemic potential and are very similar to hantaviruses, the virus family behind a current worrying outbreak, in how they spread and function. The researchers demonstrated how harnessing T cells could be critical to designing vaccines that can combat many different species of virus at once, an approach that could be applied to other viral families as well. BARDA is working with US-based company Mapp Biopharmaceutical to supply its experimental Ebola treatment for potential use in people who may have been exposed in the current outbreak of Bundibugyo ebolavirus, a strain for which there are no specific vaccines or treatments available. Mapp’s investigational monoclonal antibody treatment was developed through a longstanding public-private partnership supported by BARDA to address Ebola Sudan, which is closely related to other ebolaviruses, Laboratory studies suggest the treatment has the potential to be effective against the Bundibugyo strain.