New York, USA — 25 September 2018
GlaxoSmithKline (GSK) and Aeras announced results of an ongoing Phase 2b clinical trial of the investigational tuberculosis vaccine candidate M72/AS01E, published in the New England Journal of Medicine (NEJM). The trial demonstrated that administering two doses of M72/AS01E to HIV-negative adults with evidence of latent tuberculosis (TB) infection reduced the development of active TB disease with 54% efficacy (90% CI, 13.9 to 75.4; 95% CI, 2.9 to 78.2; P = 0.04).
The study, conducted across sites in Kenya, South Africa, and Zambia, showed protective efficacy sustained over a two-year follow-up period. The results were announced on the eve of the first-ever UN General Assembly high-level meeting on tuberculosis, held on 26 September 2018 in New York.
The First New TB Vaccine Signal in a Century
Bacillus Calmette-Guérin (BCG) is presently the only available vaccine against TB, recommended for administration to neonates as part of the Expanded Programme on Immunization. While BCG provides moderate protection against severe forms of TB in infants and young children, it does not adequately protect adolescents and adults, who account for the majority of TB transmission. The M72/AS01E candidate represents the most advanced attempt to fill this gap in nearly 100 years.
M72/AS01E is a subunit fusion protein vaccine derived from two Mycobacterium tuberculosis antigens (32A and 39A) combined with the AS01E adjuvant, designed to provide protection against active TB disease. The vaccine candidate's immunogenicity, safety, and tolerability appeared favourable in the initial report, with a full assessment expected as part of the final evaluation of the study in 2019.
Study Design and Population
The trial was a randomized, double-blind, placebo-controlled study. Participants were HIV-negative adults with evidence of latent tuberculosis infection, as determined by interferon-gamma release assay (IGRA) positivity. This population is at elevated risk of progressing from latent to active TB disease, making them a critical target for vaccine-induced protection.
The choice of study sites in Kenya, South Africa, and Zambia reflected the disproportionate burden of TB in sub-Saharan Africa. According to WHO data, the African region accounts for a significant share of the estimated 10 million people who fall ill with TB each year worldwide, with co-infection with HIV remaining a major compounding factor.
Expert Reactions
"A positive signal from this study brings us one step closer to provide a promising solution for ending TB," said Dr. Martin Friede, a.i. Director of Immunization Vaccines and Biologics at the World Health Organization (WHO). "We are hopeful that the positive results from this trial will prompt for a speedy phase 3 validation and accelerated clinical development of an effective vaccine."
Dr. Tereza Kasaeva, Director of the WHO's Global TB Programme, emphasized the broader context: "Despite the compelling global health need for a new vaccine, progress in vaccine development is significantly diminished because of the considerable and sustained resources needed to support and enhance the full continuum of R&D. We congratulate GSK and Aeras on a successful collaboration in bringing this positive result forward, and now call for strengthened engagement of public health actors to progress the field of TB vaccines."
The Global TB Burden
The WHO's End TB Strategy aims to end the global TB epidemic by 2030 and has identified "Intensified research and innovation" as a key pillar. The strategy articulates that additional tools must be available by the mid-2020s to end TB as a public health threat by 2035. A new vaccine effective pre- and post-exposure is considered critical to reduce the number of new TB cases arising from the pool of approximately 1.7 billion people worldwide who are latently infected with Mycobacterium tuberculosis.
Next Steps
Following the Phase 2b results, the vaccine candidate moved into further development. A final analysis of the same trial, with three years of follow-up, was published in the NEJM on 19 December 2019, showing an overall vaccine efficacy of 49.7% over the three-year period — confirming the durability of protection.
The WHO indicated it would issue a Q&A to inform stakeholders on the Organization's position regarding next steps, and called for strengthened engagement of public health actors to advance the field of TB vaccines. The results were presented at a time of unprecedented political attention to TB, with the UN General Assembly high-level meeting on TB representing the first time heads of state had gathered specifically to address the disease.
Sources
- WHO Departmental Update: GSK's Investigational Vaccine Candidate M72/AS01E shows promise for prevention of TB disease, 25 September 2018.
- Tait DR, Hatherill M, Van Der Meeren O, et al. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. New England Journal of Medicine, 19 December 2019.
- CIDRAP: TB vaccine candidate shows sustained protection.
- GSK Press Release: GSK candidate vaccine demonstrates sustained level of protection against active pulmonary tuberculosis.
- The Union: The Union welcomes preliminary results of new TB vaccine clinical trial.
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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.
