GSK-692342

A large Phase 3 trial will evaluate whether the M72/AS01E vaccine candidate can protect adolescents and adults from pulmonary tuberculosis Clinical trial site at University of the Witwatersrand, Johannesburg, South Africa, is first of up to 60 sites in seven countries The M72/AS01E vaccine candidate could be the first new TB vaccine in 100 years if proven effective CAMBRIDGE, Mass., March 19, 2024 /PRNewswire/ -- The Bill & Melinda Gates Medical Research Institute (Gates MRI) today announced that a Phase 3 clinical trial to assess the efficacy of the M72/AS01E tuberculosis (TB) vaccine candidate is now underway, with first doses given in South Africa, where TB takes a heavy toll. If shown to be well-tolerated and effective, M72/AS01E could potentially become the first vaccine to help prevent pulmonary TB in adolescents and adults, the most common form of the disease, and the first new TB vaccine in over a century. Globally, according to the World Health Organization, an estimated 10.6 million people fell ill with TB in 2022 and 1.3 million died — over 3,500 people per day. The disease primarily affects people in low- and middle-income countries, and those at highest risk are often living in poverty, with poor living and working conditions and undernutrition. In South Africa alone, around 280,000 people are diagnosed with TB each year. "The launch of this pivotal Phase 3 trial demonstrates our commitment to harnessing the power of medical innovation to fight diseases like TB that are particularly devastating for low- and middle-income countries," said Emilio A. Emini, Ph.D., CEO of the Gates MRI. "Clinical study of the vaccine will still require years, but our incredible partners in South Africa and elsewhere who have come together for the Phase 3 study share our hope in the vaccine's potential." The Gates MRI, a nonprofit organization and subsidiary of the Bill & Melinda Gates Foundation, is sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome. The M72/AS01E vaccine candidate has been in development since the early 2000s. It was originally designed and clinically evaluated by the biopharma company GSK up to the proof-of-concept phase (Phase 2b), in partnership with Aeras and the International AIDS Vaccine Initiative (IAVI) and was funded by GSK and in part by the Gates Foundation. In 2020, GSK announced a partnership with the Gates MRI for further development of M72/AS01E. GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the vaccine for the Phase 3 trial and will provide the adjuvant post licensure should the trial be successful. An adjuvant is an ingredient used in some vaccines that can help create a stronger immune response. Making vaccines accessible and affordable for communities in areas of high disease burden in the long-term is a priority for all trial partners. The Gates MRI has worked with a wide range of stakeholders, including communities around clinical trial sites, to guide the TB candidate vaccine to Phase 3. To this end, the Gates MRI, GSK, Wellcome and the Gates Foundation are working together to understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term sustainable access, should the trial be successful; from supporting research and building an evidence-base for the potential impact of the vaccine and community requirements for uptake, to collaborating with multilateral, regional and country partners required to introduce the vaccine. Additionally, the trial funders are planning to establish an international advisory group comprised of representatives from all these groups to provide input on the overall program. Developing and ensuring access to global health products is a complex task. As such, global collaboration and strong partnerships are a core component of planning for future access to the candidate vaccine. "Reaching Phase 3 with an urgently needed TB vaccine candidate is an important moment for South Africans because it demonstrates that there is a strong local and global commitment to fight a disease that remains distressingly common in our communities," said Dr. Lee Fairlie, Director of Maternal and Child Health at Wits RHI at University of the Witwatersrand, Johannesburg, South Africa, and national principal investigator for the trial in South Africa. "South Africa also has considerable experience with TB- and vaccine-related clinical trials and a strong track record for protecting patient safety and generating high quality data essential for regulatory approvals." At full capacity, the trial will include up to 20,000 participants, including people living with HIV, at up to 60 trial sites in seven countries — South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia and Vietnam. Participants will receive either the investigational M72/AS01E vaccine or a placebo in what is known as a double-blind trial, meaning neither the trial participant nor the clinical investigators will know who receives vaccine or placebo. This approach is considered the gold standard for evaluating the safety and efficacy of an investigational vaccine. "After dedicating over 20 years to developing this essential candidate vaccine, we at GSK are delighted that the Phase 3 trial is underway. Developing and ensuring access to global health products is complex but our collaboration with the Gates MRI, Wellcome and the Gates Foundation exemplifies the transformative power of leveraging diverse partners' expertise to change the trajectory of challenging diseases, like TB, which place a huge burden on communities around the world," said Deborah Waterhouse, CEO, ViiV Healthcare and President, Global Health, GSK. While TB is one of the world's deadliest infectious diseases — and the leading cause of death amongst people living with HIV — the only available TB vaccine, BCG, dates back to 1921. It protects babies and young children against severe forms of TB, but it offers inadequate protection for adolescents and adults against the pulmonary form of the disease, which is primarily responsible for transmission of the TB bacterium. "If effective, M72/AS01E could reinvigorate a global fight against TB that has been weakened by the COVID-19 pandemic," said Alemnew Dagnew, M.D., who leads development of M72/AS01E at the Gates MRI. "I am particularly excited to see this trial get underway because when I was working as a physician in Ethiopia, I saw first-hand what pulmonary TB does to communities — and a vaccine that could help prevent that from happening would be transformative." Dagnew noted that TB is both a health problem and a socioeconomic problem. He said the disease primarily affects people during their prime working years, leaving families without income and children without parents. Almost half of TB-affected households face costs higher than 20% of their household income. "We must continue to move with urgency to develop and equitably deliver innovative tools with the potential to transform the prevention, diagnosis, and treatment of TB. The start of the Gates MRI's M72 TB vaccine candidate Phase 3 clinical trial marks a pivotal moment in the fight to end TB, which devastatingly afflicts the world's most vulnerable communities. We think this trial marks the beginning of a series of opportunities that will usher in the most promising pipeline ever of new TB tools. The Gates Foundation remains committed to supporting local and global partners to accelerate the solutions needed to save lives and reduce suffering from this preventable disease," said Trevor Mundel, President, Global Health, Bill & Melinda Gates Foundation. Alex Pym, Director of Infectious Disease at Wellcome, said: "While it is a long journey to results, the start of this trial in South Africa brings us a critical step closer to having an effective vaccine to protect those most at risk of TB. Global collaboration with regulators, in-country decision makers and communities affected is crucial if those who need it most are to benefit from this vaccine, should the trial be successful." It is anticipated that it will take up to five years to complete the trial, followed by data analysis and then preparation for submission of data to regulatory authorities. In GSK's Phase 2b trial, M72/AS01E provided approximately 50% protection (13/1626 versus 26/1663) against progression to active pulmonary tuberculosis for three years in Mycobacterium tuberculosis-infected HIV-negative adults, which was unprecedented in decades of TB vaccine research. The World Health Organization estimates that over a 25-year time span, that level of protection could save 8.5 million lives, prevent 76 million new TB cases and save $41.5 billion for TB affected households. About the Bill & Melinda Gates Medical Research Institute (Gates MRI) The Bill & Melinda Gates Medical Research Institute is a non-profit medical research organization dedicated to the development and effective use of novel biomedical interventions addressing substantial global health concerns, for which investment incentives are limited, including malaria, tuberculosis, enteric and diarrheal diseases, and diseases that impact maternal, newborn, and child health. For further information please visit . For more information, contact: [email protected] Logo -

TB is one of the world's deadliest diseases, killing about 4,300 people per day, mostly those living in poverty LONDON and SEATTLE, June 28, 2023 /PRNewswire/ -- Wellcome and the Bill & Melinda Gates Foundation today announced funding to advance a tuberculosis (TB) vaccine candidate, M72/AS01E (M72), through a Phase III clinical trial. If proven effective, M72 could potentially become the first new vaccine to help prevent pulmonary TB, a form of active TB, in more than 100 years. In 2021, an estimated 10.6 million people fell ill with TB and 1.6 million died—about 4,300 people per day. The disease primarily affects people in low- and middle-income countries, and those at highest risk are often living in poverty, with poor living and working conditions and undernutrition. Up to a quarter of the world's population is thought to have latent TB, a condition in which a person is infected with the bacterium that causes TB but does not have any symptoms and is at risk of progressing to active TB disease. "Despite being curable, TB remains one of the leading causes of death in South Africa," said Nomathamsanqa Majozi, head of public engagement at Africa Health Research Institute. "In the area where I live and work, more than half of all people have had, or will have, TB at some point in their lives. The consequences are devastating, both at a personal and a community level. M72 offers us new hope for a TB-free future." To support the M72 Phase III clinical trial, which will cost an estimated US$550 million, Wellcome is providing up to US$150 million and the Gates Foundation will fund the remainder, about US$400 million. "TB remains one of the world's deadliest infectious diseases," said Julia Gillard, chair of the Board of Governors at Wellcome. "The development of an affordable, accessible vaccine for adults and adolescents would be game-changing in turning the tide against TB. Philanthropy can be a catalyst to drive progress, as shown by this funding of the M72 vaccine as a potential new tool in preventing escalating infectious diseases to protect those most affected. Sustainable progress against TB and wider disease threats will depend on global collaboration, financial backing, and political will. By working with communities and researchers in countries with a high burden of the disease, we can get one step closer to eliminating TB as a public health threat." The only TB vaccine in use today, bacille Calmette-Guérin (BCG), was first given to people in 1921. It helps protect babies and young children against severe systemic forms of TB but offers limited protection against pulmonary TB among adolescents and adults. "With TB cases and deaths on the rise, the need for new tools has never been more urgent," said Bill Gates, co-chair of the Bill & Melinda Gates Foundation. "Greater investment in safe and effective TB vaccines alongside a suite of new diagnostics and treatments could transform TB care for millions of people, saving lives and lowering the burden of this devastating and costly disease." Over 25 years, a vaccine with at least 50% efficacy could prevent up to 76 million new TB cases and 8.5 million deaths, avert the need for 42 million courses of antibiotic treatment, and prevent US$41.5 billion in TB-related catastrophic household costs, especially for the world's poorest and most vulnerable people, according to the World Health Organization (WHO).* The Phase III clinical trial to assess the candidate vaccine's efficacy at preventing progression from latent TB infection to pulmonary TB will be sponsored by the Bill & Melinda Gates Medical Research Institute (the Gates MRI), a nonprofit organization and subsidiary of the Gates Foundation dedicated to the development and effective use of novel biomedical interventions to address substantial global health concerns. Conducted in collaboration with an international consortium of TB clinical investigators, the trial will enroll approximately 26,000 people, including people living with HIV and without TB infection, at more than 50 trial sites in Africa and Southeast Asia. Additional details about the trial design and participants will be announced by the Gates MRI in the coming months. The Gates MRI is the license holder for M72 in low- and middle-income countries with high TB burden. The M72 vaccine candidate, one of 17 TB vaccine candidates currently in the pipeline, has been in development since the early 2000s. It was developed by GSK up to the proof-of-concept phase (Phase IIb), in partnership with Aeras and the International AIDS Vaccine Initiative (IAVI), and was funded in part by the Gates Foundation. In the Phase IIb trial, M72 showed approximately 50% efficacy in reducing pulmonary TB in adults with latent TB infection—an unprecedented result in decades of TB vaccine research. WHO Director-General Dr. Tedros Adhanom Ghebreyesus said the support by the Gates Foundation and Wellcome to develop a new TB vaccine, and the opportunity of September's UN high-level meeting on TB, shows the world can turn the tide on the TB crisis through sustained political and financial action. "The tuberculosis crisis demands a new vaccine to reduce disease transmission and avoidable death, especially targeting adults and adolescents who carry at least 90% of the TB epidemic's burden," said Dr. Tedros. "WHO welcomes the commitments from the Bill & Melinda Gates Foundation and Wellcome to take forward development of this vaccine candidate, and WHO will keep supporting vaccine development and access more broadly through its TB Vaccine Accelerator Council." * For more information about the value proposition for new tuberculosis vaccines, see the WHO-commissioned "An Investment Case for New Tuberculosis Vaccines." Note for Editors About the Vaccine Candidate The M72/AS01E vaccine candidate contains the M72 recombinant fusion protein, which is derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A), combined with the GSK proprietary Adjuvant System AS01E. The vaccine candidate was developed up to the proof-of-concept phase by GSK in conjunction with Aeras and IAVI. In 2020, GSK announced that it would partner with the Gates MRI for continued development and potential use of the M72 candidate vaccine in countries with high TB burden. GSK will continue to provide the adjuvant for the candidate vaccine's further development and potential launch. Funding for the research that uncovered the potential of M72 was provided by the United Kingdom's Department for International Development, the Directorate-General for International Cooperation in the Netherlands, the Australian Department for Foreign Affairs and Trade, the European Commission, and the Bill & Melinda Gates Foundation. About Tuberculosis TB causes more deaths annually than any other infectious disease, with an estimated 10.6 million new cases and 1.6 million deaths in 2021. The COVID-19 pandemic reversed progress against TB and revealed the fragility of the steady gains made over the previous 20 years in expanding access to prevention, testing, and treatment. In 2021, during the pandemic, TB cases increased by 4.5% compared to those reported in 2020, and fewer people were diagnosed or received treatment. To get back on track to achieving the 2030 United Nations Sustainable Development Goals target of an 80% reduction in the TB incidence rate compared with 2015, the world urgently needs new tools to combat this disease. TB is also the leading killer of people living with HIV, accounting for one-third of deaths among HIV-positive people. The world's most vulnerable populations are disproportionately affected by TB, with many cases of TB occurring in resource-limited areas. Over 80% of cases and deaths are in low- and middle-income countries. About TB Research and Development After 20 years of increased investment in research and development (R&D), the TB innovation pipeline is strengthening, with new tools that have the potential to accelerate progress toward the 2030 global target. The pipeline includes novel diagnostic tests and sample collection methods, as well as shorter drug regimens for TB and drug-resistant TB. But ending TB as a global health burden can only be achieved with the development and deployment of an effective vaccine for adolescents and adults. Additional R&D investments in effective diagnostics and vaccines and shorter drug regimens are needed to accelerate progress against TB. According to the Global Plan to End TB 2023-2030, more than US$26 billion is needed each year from 2023 to 2030 to scale up TB care and prevention services for all people in need. TB R&D will require an additional US$5 billion per year during that period. Global backing, both financial and political, is necessary to drive innovation and develop, manufacture, and deliver a robust pipeline of TB diagnostics, treatments, and vaccines to save and protect millions of lives from TB. About Wellcome Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we're taking on three worldwide health challenges: mental health, infectious disease and climate and health. Media contact: [email protected] About the Bill & Melinda Gates Foundation Guided by the belief that every life has equal value, the Bill & Melinda Gates Foundation works to help all people lead healthy, productive lives. In developing countries, it focuses on improving people's health and giving them the chance to lift themselves out of hunger and extreme poverty. In the United States, it seeks to ensure that all people—especially those with the fewest resources—have access to the opportunities they need to succeed in school and life. Based in Seattle, Washington, the foundation is led by CEO Mark Suzman, under the direction of Co-chairs Bill Gates and Melinda French Gates and the board of trustees. Media contact: [email protected] Additional Quotes Emilio Emini, CEO of the Bill & Melinda Gates Medical Research Institute: "The Bill & Melinda Gates Medical Research Institute is committed to developing biomedical interventions that address global health concerns for those in the greatest need. We look forward to partnering with a team of investigators across international study sites to assess the potential of the candidate vaccine in preventing pulmonary TB in adolescents and adults." Thomas Breuer, chief global health officer at GSK: "This is an important moment for those working to get ahead of TB. The Gates Foundation and Wellcome's funding is critical for the further development of the candidate vaccine. At GSK, we remain committed to the long-term success of the M72 candidate vaccine, including through the continued supply of our proprietary adjuvant, AS01E, for people at risk of TB in lower-income countries." Mark Harrington, executive director of Treatment Action Group (TAG): "TAG welcomes this historic investment in TB vaccine development by Wellcome and the Bill & Melinda Gates Foundation. A Phase III clinical trial of the M72/AS01E TB vaccine candidate is a long-awaited milestone. We hope this funding commitment sparks governments and other funders to substantially increase investments in the TB vaccine pipeline, which contains a number of promising candidates in addition to M72/AS01E but faces a dire financial shortfall. This Phase III trial will take several years to complete. We encourage the Gates Foundation, Wellcome, GSK, country governments, and other partners to use this time to lay the groundwork for eventual vaccine adoption by ensuring the availability, affordability, and acceptability of M72/AS01E should it prove safe and effective." Patrick Agbassi, chair of the Global TB Community Advisory Board (TB CAB): "We've waited a long time for this study, so are happy to see the Bill & Melinda Gates Foundation and Wellcome taking up this important task. The question now becomes how we can enroll 26,000 people most quickly and ensure that all populations at risk of TB will ultimately be able to benefit from access to what could be the first new TB vaccine in over 100 years. A robust community engagement program will be key, as will taking on studying this vaccine in younger adolescents, pregnant women, people with prior history of TB, and other key groups often underrepresented or left out entirely of TB trials and the benefits of scientific progress." SOURCE Bill & Melinda Gates Foundation