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Seattle, USA · June 2025 — The Phase 3 clinical trial of the M72/AS01E tuberculosis vaccine candidate, sponsored by the Gates Medical Research Institute (Gates MRI), reached a critical milestone in April 2025 when it successfully achieved full enrollment of approximately 20,080 participants. The trial, conducted across 54 sites in five countries, represents the most advanced effort to develop a new tuberculosis vaccine in more than a century.
The enrollment milestone, announced by Gates MRI, marked a pivotal moment in the global fight against tuberculosis — a disease that killed an estimated 1.25 million people in 2023 and sickened 10.6 million, according to the WHO Global Tuberculosis Report 2024.
A Century-Long Wait for a New Vaccine
The only tuberculosis vaccine currently in use — Bacille Calmette-Guérin (BCG) — was first administered in 1921. While BCG provides some protection against severe forms of TB in young children, its efficacy against pulmonary TB in adolescents and adults — the primary drivers of transmission — is variable and generally poor. For over a century, no new TB vaccine has completed development and entered widespread use.
M72/AS01E is considered one of the most promising candidates in the TB vaccine pipeline. A previous Phase 2b trial, conducted by GSK with support from Aeras and the Bill & Melinda Gates Foundation, suggested approximately 50% efficacy in preventing the progression to active pulmonary TB in TB-infected, HIV-negative adults. The Phase 3 trial is designed to confirm whether this efficacy holds at scale.
Trial Design and Scope
The M72/AS01E Phase 3 trial (registered as NCT06062238 on ClinicalTrials.gov) is a randomized, double-blind, placebo-controlled study designed to assess the safety, immunogenicity, and prophylactic efficacy of the vaccine candidate in preventing pulmonary tuberculosis in adolescents and adults.
| Parameter | Detail |
|---|---|
| Sponsor | Gates Medical Research Institute |
| Design | Randomized, double-blind, placebo-controlled |
| Enrollment | ~20,080 participants |
| Sites | 54 clinical sites across 5 countries |
| Countries | South Africa, Kenya, Malawi, Zambia, Indonesia |
| Primary endpoint | Prevention of pulmonary TB |
| Estimated primary completion | April 2028 |
| Population | Adolescents and adults |
The geographic spread of the trial sites reflects the global distribution of the TB burden. South Africa, Kenya, Malawi, and Zambia all face significant TB epidemics, compounded in many cases by HIV co-infection. Indonesia, the second-highest TB burden country globally after India, brings the trial into the Southeast Asian context where TB control faces distinct challenges related to geography, health system structure, and drug resistance.
The Road to Phase 3
The M72/AS01E vaccine candidate has a complex development history. Originally developed by GSK using the AS01E adjuvant system, the candidate showed promise in early-phase trials. In 2020, GSK licensed the vaccine candidate to the Gates Medical Research Institute for further development, with the goal of advancing it through Phase 3 testing and, if successful, toward regulatory submission and global availability.
The Gates MRI, a non-profit biotechnology organization, took on the sponsorship with a mission to develop biomedical interventions for diseases that disproportionately affect the world's poorest populations. The transition from GSK to Gates MRI ensured that the vaccine candidate would be developed with a focus on accessibility and affordability for low- and middle-income countries, rather than commercial returns.
A prior article in this publication covered the March 2024 launch of the Phase 3 trial. The achievement of full enrollment just over a year later reflects the extraordinary commitment of trial site investigators, community engagement teams, and the participants themselves — many of whom traveled significant distances to attend clinic visits in settings with limited healthcare infrastructure.
Preparing for Manufacturing
While the trial is still underway, significant steps have been taken to prepare for potential deployment. In July 2026, Gates MRI announced a milestone agreement with the Serum Institute of India (SII) — the world's largest vaccine manufacturer — to manufacture the M72/AS01E vaccine candidate, pending successful Phase 3 outcomes.
This proactive manufacturing preparation is intended to ensure that, if the vaccine is approved, it can be produced at scale and distributed to high-burden countries as quickly as possible. The agreement with SII reflects lessons learned from other vaccine introductions, where manufacturing delays created bottlenecks between regulatory approval and population-level access.
The Global TB Context
The M72/AS01E trial proceeds against a backdrop of persistent challenges in global TB control:
- Mortality: An estimated 1.25 million people died from TB in 2023, including 161,000 among people living with HIV
- Incidence: 10.6 million people fell ill with TB worldwide in 2023
- Drug resistance: 400,000 people developed multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) in 2023
- Funding gap: Global TB research and development funding consistently falls short of the targets set at the UN High-Level Meetings on TB
The COVID-19 pandemic dealt a severe blow to TB programs worldwide, disrupting diagnosis and treatment services and causing a temporary increase in TB deaths. While TB programs have largely recovered, the pandemic's impact on underlying TB epidemiology — through delayed diagnoses and interrupted treatment — continues to be felt.
What Comes Next
With enrollment complete, the trial now enters its follow-up phase, during which participants will be monitored for the development of pulmonary TB. The primary analysis will compare TB incidence between the vaccine and placebo groups, with the trial estimated to reach its primary completion date in April 2028.
If the results confirm the efficacy signal observed in Phase 2b, the pathway to regulatory submission and WHO prequalification would follow. Given the manufacturing agreement with SII, the vaccine could potentially be available for introduction in high-burden countries within a few years of approval — though the exact timeline would depend on regulatory processes, pricing negotiations, and country-level adoption decisions.
The TB vaccine community has learned from the malaria vaccine experience that introducing a new vaccine into routine immunization programs requires years of planning, financing, and political commitment. The M72/AS01E trial's progress offers hope, but the work of ensuring that an effective vaccine reaches the populations who need it most has only just begun.
Sources
- Gates Medical Research Institute, "The Phase 3 clinical trial of the M72/AS01E tuberculosis vaccine candidate has reached full enrollment," April 2025 —
- ClinicalTrials.gov, NCT06062238 —
- Wellcome, "Manufacturer agreed for M72/AS01E TB vaccine candidate, pending trial outcomes," 2026 —
- Gates MRI, "Gates Medical Research Institute and the Serum Institute of India reach agreement," July 2026 —
- WHO, Global Tuberculosis Report 2024 —
- New TB Vaccines, M72/AS01E profile —
FIRAT Editorial Board
Institutional Research Desk · Foresight Institute of Research and Translation
The collective editorial and research translation board of FIRAT, synthesising peer-reviewed evidence, policy briefs, and division milestones across our seven foundational research pillars.
