Cape Town, South Africa · 21 March 2025
A Phase 3 clinical trial of the M72/AS01E tuberculosis vaccine candidate is running a full year ahead of schedule and has already enrolled more than 90% of its 20,000 participants, according to Dr Alemnew Dagnew, who leads the vaccine's clinical development at the Gates Medical Research Institute (Gates MRI).
The trial, which began in March 2024, was initially projected to take two years for full enrollment across 54 sites in South Africa, Kenya, Zambia, Malawi, and Indonesia. Instead, researchers expect to complete enrollment within weeks — a pace that reflects both the urgency of the TB burden in trial communities and the research infrastructure established in high-incidence settings.
Why 50% Efficacy Matters
A Phase 2b trial of M72/AS01E, published in the New England Journal of Medicine in 2018 and 2019, found the vaccine was approximately 50% effective in preventing adolescents and adults already infected with latent TB from developing pulmonary TB. For many diseases, 50% efficacy would be considered insufficient to justify a costly Phase 3 programme. For tuberculosis, the calculus is different.
Tuberculosis remains one of the world's most deadly infectious diseases. The only currently available TB vaccine is BCG, first administered to humans in 1921 — over a century ago. While BCG works well in preventing severe forms of childhood TB, its efficacy against pulmonary TB in adolescents and adults is insignificant. No new TB vaccine has been developed since, despite TB killing approximately 1.25 million people globally in 2023.
Trial Design and Population
The M72/AS01E vaccine is composed of a fusion of two TB antigens combined with GSK's AS01 adjuvant, which boosts the body's immune response. Trial participants receive two doses of the vaccine or a placebo 28 days apart, with telephonic follow-up every two months and a clinic visit every six months until the trial concludes.
The 20,000 participants reflect the populations most affected by TB:
- 18,000 participants are infected with latent TB — meaning they carry the bacteria but are not symptomatic or infectious
- 1,000 participants are non-TB infected
- 1,000 participants are people living with HIV
Sites were selected because they are in communities with high TB incidence and because of the countries' capability to conduct clinical research, according to Dr Dagnew.
From GSK to Gates MRI
The vaccine was first developed by GSK over many years. After the Phase 2b results demonstrated promising efficacy, Gates MRI stepped in to license the vaccine candidate and sponsor the Phase 3 trial, with funding from the Gates Foundation and Wellcome Trust.
GSK continues to provide the adjuvant component for clinical trials and has committed to supplying it for the commercial product if the Phase 3 trial succeeds. The company has also been working with Gates MRI on technology transfer to manufacture the antigen component — a critical step toward ensuring affordable, large-scale production if the vaccine is approved.
A Personal Mission
Dr Dagnew, who was born and raised in Ethiopia and trained as a physician there, described the trial in deeply personal terms:
"One of the most common health conditions that I used to manage was TB, so I have seen the devastating impact of TB on patients, their families and also the communities. TB affects people of poor socio-economic status. If a family member gets sick with TB, then they would have to stop working. If that family member is the only source of income, the whole family will be in a bad situation. Developing a vaccine like the one which I'm currently working on, [if successful] is going to be like a gift to the community that I came from."
The Century-Long Wait
The BCG vaccine was developed at the Pasteur Institute in Lille, France, by Albert Calmette and Camille Guérin, and was first given to a human infant on 18 July 1921. In the 104 years since, despite TB killing tens of millions of people, no new vaccine has completed development.
The M72/AS01E Phase 3 trial represents the most advanced attempt to break that century-long drought. If the trial demonstrates efficacy — results are not expected before the primary completion date, estimated for 2028 — the vaccine would be the first to protect adolescents and adults against pulmonary TB, the most common and transmissible form of the disease.
What Comes Next
If the Phase 3 trial succeeds, the path to regulatory approval, manufacturing scale-up, and integration into national immunisation programmes will require sustained investment and political will. The technology transfer arrangements already underway between GSK and Gates MRI for antigen manufacturing represent a proactive strategy to ensure that, upon approval, production capacity can meet global demand — particularly in the high-burden countries where the vaccine was tested.
For now, the research community watches the enrollment numbers with cautious optimism. The acceleration of enrollment is a logistical achievement, but the scientific question remains unchanged: can M72/AS01E replicate its Phase 2b promise at scale, across diverse populations, and under real-world conditions? The answer will determine whether the century-long wait for a new TB vaccine is finally nearing its end.
Sources:
- Health Policy Watch, "Promising Phase 3 Trial of Tuberculosis Vaccine is Running Ahead of Schedule," 21 March 2025.
- ClinicalTrials.gov, NCT06062238.
- Wellcome Trust, M72/AS01E TB vaccine candidate.
- Gates Medical Research Institute.
- New England Journal of Medicine, Phase 2b M72/AS01E results (2018, 2019).
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.
