M72/AS01E (M72) Tuberculosis Vaccine Candidate Clinical Trials, Dosage, News, Side Effects, Usage

M72/AS01E (M72) is a subunit vaccine candidate that contains the M72 recombinant fusion protein derived from two Mycobacterium tuberculosis (Mtb) antigens (Mtb32A and Mtb39A) combined with the GlaxoSmithKline plc (GSK) proprietary Adjuvant System AS01. The Mtb39A and Mtb32A components of the recombinant antigen elicited specific lymphoproliferation and/or interferon-gamma (IFN-γ) production in individuals with latent and active TB. AS01E is the adjuvant in GSK's Shingrix® shingles and Mosquirix™ (RTS,S) vaccines. M72/AS01E is indicated to prevent Pulmonary Tuberculosis (TB) in adolescents and adults.

The M72/AS01E vaccine candidate has been developing since the early 2000s. In 2020, GSK announced a partnership with the Gates Medical Research Institute (Gate MRI) for further development of M72/AS01E. GSK licensed M72 to the Gates MRI. An adjuvant is an ingredient in some vaccines that can help create a more robust immune response. GSK retains ownership of the adjuvant. It was initially 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 Bill & Melinda Gates Foundation. In the Phase 2b clinical trial, this vaccine candidate provided approximately 54% protection against progression to active pulmonary TB for three years in TB-infected HIV-negative adults.

GSK continues to provide technical assistance to the Gates MRI, supplying the adjuvant component of the vaccine for the Phase 3 trial (NCT06062238), launched in March 2024, and will provide the adjuvant post-licensure should the trial be successful. The Estimated Primary Completion Date of this study is April 2028. If M72/AS01E is approved, it could be the first new TB vaccine in 100 years.

On June 28, 2023, Wellcome and the Gates Foundation announced funding to advance M72/AS01E (M72) through a Phase 3 clinical trial. To support the M72 Phase 3 clinical trial, which will cost an estimated $550 million, Wellcome is providing up to $150 million, and the Gates MRI, a subsidiary of the Gates Foundation, will fund the remainder, about $400 million. On March 19, 2024, Gates MRI announced that the Phase 3 clinical trial was underway at the University of the Witwatersrand, Johannesburg, South Africa, the first of up to 60 study sites in seven countries, recruiting about 26,000 participants.

M72/AS01E (M72) Tuberculosis Vaccine Indication

The WHO says TB is a preventable and curable disease that 25% of the global population is estimated to be infected with Mycobacterium tuberculosis. TB is the leading infectious cause of death worldwide. The BCG vaccine helps protect young children against severe systemic forms of TB but offers limited protection against pulmonary TB among adolescents and adults.

M72/AS01E (M72) Tuberculosis Vaccine Dosage

M72/AS01E two doses are administered intramuscularly in the deltoid region of the arm.

M72/AS01E (M72) Tuberculosis Vaccine News

March 19, 2024 - "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," said Emilio A. Emini, Ph.D., CEO of the Gates MRI.

November 16, 2023 - Nicole Frahm, Ph.D. Head of Biomarker Development presented Immune Correlates of Protection for BCG and M72 TB Vaccines.

November 16, 2023 - Linda Han, MD, MPH, presented: Safety and immunogenicity of the investigational TB vaccine M72/AS01E-4 in people living with HIV.

June 28, 2023 - Bill Gates, the co-chair of the Bill & Melinda Gates Foundation, commented in a press release, "Greater investment in safe and effective TB vaccines alongside a suite of new diagnostics and treatments could transform TB care for millions of people, saving lives and lowering the burden of this devastating and costly disease."

May 10, 2022 - AFP reported that the M72 TB vaccine could save tens of thousands of South African lives yearly.

December 20, 2021 - A Multi-country, Epidemiologic Study to Assess the Interferon Gamma Release Assay Positivity and Build Capacity to Conduct a TB Vaccine Efficacy Study in Populations With a High TB Disease Burden.

June 30, 2020 - The WHO published - Vaccines and Immunization: Investigational vaccine candidate M72/AS01E: FAQs.

January 27, 2020 - GSK plc announced that it had licensed its M72/AS01E TB vaccine candidate to the Bill & Melinda Gates Medical Research Institute. Trevor Mundel, President of Global Health at the Bill & Melinda Gates Foundation. "Discovering and developing a new TB vaccine is a Gates Foundation priority, and we look forward to working in partnership with stakeholders in the global health community towards this goal."

October 29, 2019 -  GSK and IAVI reported that GSK's M72/AS01E candidate vaccine significantly reduced the incidence of pulmonary TB in HIV-negative adults with latent TB infection. These results demonstrate an overall vaccine efficacy of 50% during the three years after vaccination. In addition, the candidate vaccine has an acceptable safety and reactogenicity profile.

September 25, 2018 - Results from the Phase 2b Controlled Trial of M72/AS01 E Vaccine to Prevent Tuberculosis. Conclusions: M72/AS01E provided 54% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease without evident safety concerns. 

M72/AS01E Clinical Trials

Clinical Trial NCT01755598: Study to Evaluate the Efficacy of GlaxoSmithKline Biologicals' Candidate TB Vaccine in Adults. The results showed that administering two doses of M72/AS01E successfully reduced the development of active TB disease with 50% efficacy (90% CI, 12 to 71) in HIV-negative adults with latent Mycobacterium tuberculosis infection. A total of 39 participants contributed to the primary vaccine efficacy analysis during three years of follow-up: 13 participants vaccinated with M72/AS01E developed pulmonary TB compared to 26 participants in the placebo group.

Clinical Trial NCT06062238: TBV02-301, was First Posted on October 2, 2023 - 20,000 adolescents and adults will be randomized 1:1 to receive two doses of M72/AS01E or placebo. The primary endpoint: preventing bacteriologically confirmed pulmonary TB. This trial will be conducted in 3 cohorts: Interferon gamma release assay-positive Cohort, IGRA-Negative Cohort, and HIV Cohort.