On March 19th, the Bill & Melinda Gates Medical Research Institute (Gates MRI) announced that it had launched a Phase 3 clinical trial to evaluate the efficacy of a tuberculosis (TB) vaccine candidate, M72/AS01E (M72), with the first vaccinations taking place in South Africa, where TB is a leading cause of illness. If proven to be safe and effective, M72 has the potential to become the first vaccine to prevent the most common form of TB in adolescents and adults and the first new TB vaccine in over a century.
According to the World Health Organization, an estimated 10.6 million people fell ill with TB and 1.3 million died from the disease in 2022—more than 3,500 people every day. TB primarily affects people living in low- and middle-income countries, and poor and marginalized people living in crowded conditions and with poor nutrition are at highest risk of developing the disease. In South Africa alone, an estimated 280,000 people are diagnosed with TB each year.
“We are committed to using the power of medical innovation to fight TB and other diseases that disproportionately affect low- and middle-income countries, and this launch of a pivotal Phase 3 trial is a testament to that commitment,” said Emilio A. Emini, PhD, MPH, CEO of Gates MRI. “While the clinical studies of the M72 vaccine could take several years to complete, we are excited about the potential of M72 and grateful to our outstanding partners who are conducting the Phase 3 trials in South Africa and beyond.”
Lee Fairlie, PhD, Director of Maternal and Child Health Research Unit, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa, is the principal investigator for the clinical trial site in South Africa. “TB remains a major public health concern in South Africa, and the need for a vaccine candidate like M72 is urgent,” she said. “The initiation of a Phase 3 clinical trial is a significant moment for the people of South Africa, and reflects the strength of local and global commitment to TB research. South Africa has a wealth of experience in TB and vaccine clinical trials and an established track record for ensuring patient safety while generating high-quality data that are critical for regulatory approvals.”
If fully enrolled, the trial will include up to 20,000 participants, including people living with HIV who are not infected with TB, across 60 sites in seven countries: South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia, and Vietnam. Participants will be randomized in a double-blind fashion to receive either the M72/AS01E vaccine or a placebo, meaning that neither the participants nor the clinical research team will know who is receiving the vaccine and who is receiving the placebo. This approach is considered the gold standard for evaluating the safety and efficacy of vaccines.
TB is the world’s deadliest infectious disease and a leading cause of death for people with HIV. The BCG vaccine is the only TB vaccine currently in use, having first been given to humans in 1921. It protects young children from severe, disseminated forms of TB, but it has limited efficacy against pulmonary TB in adolescents and adults, the form of TB that is responsible for most transmission.
“If proven effective, M72/AS01E would be a major boost to the global fight against TB at a time when progress has stalled due to COVID-19,” said Alemnew Dagnew, MD, MPH, Director of M72/AS01E Development at Gates MRI. “I am particularly excited to see this trial launch, having witnessed firsthand the devastating impact pulmonary TB can have on communities in my home country of Ethiopia, where a vaccine to prevent such suffering would be revolutionary.”
Dr. Dagnew emphasized that TB is as much a socioeconomic issue as a health issue, noting that TB primarily affects people in their prime working years, leading to loss of income for families and loss of parents for children. Nearly half of all households affected by TB experience catastrophic health expenditures, spending more than 20% of their household income on medical care.
“Urgent action is needed to develop and equitably deliver transformative tools for TB prevention, diagnosis, and treatment, as TB takes a devastating toll on the world’s most vulnerable communities. The Gates MRI-led Phase 3 clinical trial of the M72 TB vaccine candidate marks a pivotal moment in the fight to end TB, and we are optimistic that this trial will be the first of many that will bring us closer to the new TB prevention tools that the world urgently needs,” said Trevor Mundel, President of Global Health at the Bill & Melinda Gates Foundation.
The trial is expected to last five years, followed by data analysis and submission to regulatory authorities. The trial is funded by the Bill & Melinda Gates Foundation and the Wellcome Trust. The M72 vaccine candidate’s development began in the early 2000s and, prior to the proof-of-concept (Phase 2b) study, was supported by a collaboration between GlaxoSmithKline, Aeras, the International AIDS Vaccine Initiative (IAVI), and the Gates Foundation.
In GSK’s Phase 2b trial, M72/AS01E provided approximately 50% protection (13/1626 versus 26/1663) against progression to active pulmonary TB over three years in HIV-negative people infected with M. tuberculosis, an unprecedented level of efficacy for a TB vaccine. The World Health Organization estimates that over a 25-year period, the vaccine could avert 8.5 million deaths, prevent 76 million new cases, and save $41.5 billion USD for households affected by TB.
