Breakthroughs Blog: Research Roundup

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. 

On Thursday, the World Health Organization (WHO) announced the first patient enrollment in a critical clinical trial evaluating investigational antiviral therapies to treat Ebola caused by the Bundibugyo virus, as the worrying outbreak in the Democratic Republic of the Congo continues to grow. There are currently no approved treatments specifically for the Bundibugyo strain. The trial is supported by a range of multilateral, regional, national, and scientific partners and is being coordinated by the Institut National de Recherche Biomédicale, the Institute of Tropical Medicine and the University of Oxford. Two therapies, the monoclonal antibody MBP134 and remdesivir, which were selected by WHO technical advisors, are being evaluated for their ability to improve survival among patients, with the goal of saving lives and helping curb the spread of the current outbreak, as well as generating evidence to improve care for future outbreaks. A comprehensive review of COVID-19 mRNA vaccines published last week in The Lancet found that they are safe and effective, as skepticism around the safety and trustworthiness of the technology has persisted in recent years, while new research efforts have demonstrated the technology’s promise to address a range of priority disease and health challenges, including influenza and cancer. The researchers found that serious events are rare and the odds of them occurring were outweighed by significant protection against severe disease, hospitalization, and death. The researchers do acknowledge challenges with mRNA technology, including that they mRNA vaccines are not as effective at providing long-last immunity as they are at generating short-term responses and they have significant, expensive storage resource requirements, challenging access in low-resource areas. Sustained innovation and a commitment to improving access could help address these shortcomings and ensure the promise of mRNA technology is fully realized around the world.Early results from a new study published in Nature last week found that an investigational HIV vaccine demonstrated unprecedented success in primates in a preclinical trial. The vaccine, which was developed through a prolonged collaboration between scientists at La Jolla Institute for Immunology and Scripps Research, works by prompting the immune system to produce high numbers of broadly neutralizing antibodies, which are capable of neutralizing a wide range of strains of the virus and are recognized as a promising approach in the HIV vaccine development field. One of the challenges of developing a vaccine for HIV has been the genetic diversity of the virus, with various distinct strains circulating. People living with HIV naturally develop broadly neutralizing antibodies that can neutralize various strains but designing a vaccine that can induce them has proven to be a challenge for researchers. 

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.