The Bill & Melinda Gates Medical Research Institute (Gates MRI) announced on March 19th that they are initiating a Phase 3 clinical trial in South Africa, a country heavily burdened by tuberculosis (TB), to evaluate the efficacy of a candidate TB vaccine, M72/AS01E (M72). If proven safe and effective, M72 could potentially become the first vaccine to prevent the most common form of TB in both adolescents and adults and would be the first new vaccine for TB in over a century.
According to the World Health Organization, an estimated 10.6 million people fell ill with TB in 2022, and 1.3 million died from the disease – meaning more than 3,500 people die each day from TB. The disease disproportionately affects people living in low- and middle-income countries, with the highest risk found among poor and vulnerable populations living and working in crowded and unsanitary conditions and with limited access to nutrition. In South Africa alone, an estimated 280,000 people are diagnosed with TB each year.
“We are committed to harnessing the power of medical innovation to fight TB and other diseases that exact a huge toll in low- and middle-income countries. The launch of this pivotal Phase 3 trial is a testament to that commitment,” said Gates MRI CEO and Director Dr. Emilio A. Emini. “While it will be several years before we know whether the M72 vaccine is safe and effective, the extraordinary partners working with us in South Africa and beyond give us great hope for its potential.”
Dr. Lee Fairlie, head of the Wits Reproductive Health and HIV Institute at the University of the Witwatersrand (Wits RHI) in Johannesburg, South Africa, is the principal investigator for the clinical trial site in South Africa. She said, “TB remains a common and devastating disease in South Africa. The urgent need for a TB vaccine candidate like M72 and the fact that this Phase 3 trial is happening in South Africa are testaments to the strong local and global commitment and expertise that exists in the country for TB and vaccine clinical trials, with an excellent track record of ensuring participant safety and generating high-quality data that is essential for regulatory approval.”
The trial, if fully enrolled, will involve up to 20,000 participants including people living with HIV who don’t have TB infection, across 60 trial sites in seven countries: South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia, and Vietnam. Participants will be randomized to receive either the M72/AS01E vaccine or a placebo in a double-blind study, meaning neither the trial participants nor the study staff will know whether the participant received the vaccine or the placebo. This approach is considered the gold standard for evaluating the safety and efficacy of vaccines.
TB is one of the world’s deadliest infectious diseases and is the leading cause of death among people living with HIV. The only TB vaccine currently in use is called BCG, which was first used in humans in 1921. It is effective at protecting infants from severe, disseminated forms of TB but has limited efficacy against pulmonary TB in adolescents and adults, the main drivers of TB transmission.
“If proven effective, M72/AS01E could not come at a more critical time in the global fight against TB, which has been further strained by the COVID-19 pandemic,” said Gates MRI Medical Director for M72/AS01E Development, Alemnew Dagnew, MD, PhD. “I am particularly moved by the start of this trial because, as a physician in Ethiopia, I witnessed firsthand the devastation pulmonary TB brought to my community and how having a vaccine to prevent it could revolutionize health.”
Dagnew emphasizes that TB is as much a socioeconomic issue as it is a health issue. He notes that TB primarily affects people in their most productive years, depriving families of their breadwinners and children of their caregivers. Close to half of all households affected by TB experience catastrophic health expenditures, defined as spending more than 20% of their household income on medical expenses.
“We urgently need to develop and equitably deliver transformative tools that improve prevention, diagnosis, and treatment of TB, which has caused so much suffering for the world’s most vulnerable communities. Today’s launch of the Phase 3 trial of the M72 TB vaccine candidate by Gates MRI marks a critical step in the fight to end TB. We trust this trial will usher in a series of milestones that will ultimately result in the most promising new tools yet for TB control,” said Trevor Mundel, president of the Bill & Melinda Gates Foundation’s Global Health Program.
The clinical trial is anticipated to run for five years, after which data will be analyzed and submitted to regulatory authorities. The trial is funded by the Gates Foundation and the Wellcome Trust. The M72 vaccine candidate has been in development since the early 2000s, with pre-proof-of-concept (Phase IIb) development led by GlaxoSmithKline (GSK) in partnership with Aeras and the International AIDS Vaccine Initiative (IAVI), with some funding from the Gates Foundation.
In GSK’s Phase IIb trial, M72/AS01E provided approximately 50% protection (13/1626 versus 26/1663) against developing active pulmonary TB disease within three years in HIV-negative people with latent TB infection, an unprecedented level of efficacy for a TB vaccine. The World Health Organization has estimated that if the durability of protection is sustained, the vaccine could save 8.5 million lives over 25 years, avert 76 million new cases, and save TB-affected households 41.5 billion USD.
