Gates Medical Research Institute Launches Phase 3 Trial of M72/AS01E Tuberculosis Vaccine Candidate — Potential First New TB Vaccine in a Century

Cambridge, Massachusetts, USA — 19 March 2024 — The Bill & Melinda Gates Medical Research Institute (Gates MRI) announced today that a Phase 3 clinical trial to assess the efficacy of the M72/AS01E tuberculosis (TB) vaccine candidate is now underway, with the first doses administered in South Africa. If shown to be well-tolerated and effective, M72/AS01E could 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.

The clinical trial site at the University of the Witwatersrand in Johannesburg, South Africa, is the first of up to 60 sites in seven countries to begin dosing participants. The trial is sponsored by the Gates MRI, a nonprofit subsidiary of the Bill & Melinda Gates Foundation, with funding from the Gates Foundation and Wellcome.

The Burden of Tuberculosis

Tuberculosis remains one of the world's deadliest infectious diseases. 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.

TB is also the leading cause of death among people living with HIV. The only available TB vaccine, BCG (Bacille Calmette-Guérin), 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.

Trial Design and Scope

The Phase 3 trial is a randomised, double-blind, placebo-controlled, multicentre study designed to assess the efficacy, safety, and immunogenicity of the M72/AS01E vaccine candidate in preventing pulmonary tuberculosis in adolescents and adults.

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. Neither the trial participant nor the clinical investigators will know who receives vaccine or placebo — the gold standard for evaluating the safety and efficacy of an investigational vaccine.

The Development History of M72/AS01E

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 and supplies the adjuvant component of the vaccine (AS01E) for the Phase 3 trial.

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 — a result that was unprecedented in decades of TB vaccine research.

Voices from the Trial

Emilio A. Emini, Ph.D., CEO of the Gates MRI, said: "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. 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."

Dr Lee Fairlie, Director of Maternal and Child Health at Wits RHI at the University of the Witwatersrand and national principal investigator for the trial in South Africa, said: "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. 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."

Deborah Waterhouse, CEO of ViiV Healthcare and President, Global Health at GSK, said: "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."

The Socioeconomic Dimension

Alemnew Dagnew, M.D., who leads development of M72/AS01E at the Gates MRI, noted that TB is both a health problem and a socioeconomic problem. 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 due to the disease.

"If effective, M72/AS01E could reinvigorate a global fight against TB that has been weakened by the COVID-19 pandemic," Dagnew said. "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."

Ensuring Equitable Access

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.

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.

Trevor Mundel, President of Global Health at the Bill & Melinda Gates Foundation, said: "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."

Alex Pym, Director of Infectious Disease at Wellcome, added: "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."

Timeline and What Comes Next

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. Results from the Phase 3 trial are therefore not expected before 2029 at the earliest.

In April 2025, the Gates MRI announced that the trial had reached its full enrolment of approximately 20,000 participants — significantly ahead of the original schedule. In July 2026, the Gates MRI reached a milestone agreement with the Serum Institute of India (SII) to manufacture the vaccine, a proactive step to ensure that, if the Phase 3 trial proves the vaccine's efficacy and it receives regulatory approval, the vaccine can be produced at scale and distributed efficiently to high-burden countries.

Sources

• Bill & Melinda Gates Medical Research Institute, "Gates MRI Initiates Phase 3 Clinical Trial of Tuberculosis Vaccine Candidate," 19 March 2024 — gatesmri.org
• Gates MRI, "The Phase 3 clinical trial of the M72/AS01E TB vaccine candidate has reached full enrollment" — gatesmri.org
• Wellcome, "Manufacturer agreed for M72/AS01E TB vaccine candidate, pending trial outcomes" — wellcome.org
• Serum Institute of India, "Gates Medical Research Institute and the Serum Institute of India reach agreement" — seruminstitute.com
• ClinicalTrials.gov, NCT06062238 — clinicaltrials.gov
• World Health Organization, Tuberculosis Fact Sheet — who.int