Malawi has become the fifth country in the world to launch Phase 3 clinical trial sites for the M72/AS01E tuberculosis vaccine candidates. Screening for the participants began at a site in Blantyre, with a second trial site also planned.

Globally, according to the World Health Organisation, an estimated 10.8 million people fell ill with TB in 2023 and 1.25 million died — over 3,400 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. Almost half of TB-affected households face costs higher than 20% of their household income. In Malawi alone, around 25,000 people are estimated to develop TB each year.

While TB is one of the world’s deadliest infectious diseases — and the leading cause of death amongst people living with HIV — the only available TB vaccine, BCG, dates 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.

In March 2024, the Bill & Melinda Gates Medical Research Institute (Gates MRI) announced that a Phase 3 clinical trial to assess the efficacy of the M72/AS01E tuberculosis vaccine candidate was underway, with first doses given in South Africa.

In September 2024, Malawi became the fifth country to initiate clinical trial sites for the vaccine candidate, with first doses given on 23 October 2024 at a site in Blantyre. There will be a total of two clinical trial sites in Malawi, led by Professor Henry Mwandumba, the national principal investigator for the trial in Malawi.

“We have now taken the significant step of launching this TB vaccine trial in Malawi,” said Prof. Henry Mwandumba. “We are proud to contribute to this clinical trial. TB continues to pose a major public health threat to our communities, so we must stay committed to finding ways to prevent it.”

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 in what is known as a double-blind trial, meaning neither the trial participant nor the clinical investigators will know who receives vaccine or placebo. This approach is considered the gold standard for evaluating the safety and efficacy of an investigational vaccine.

If shown to be well-tolerated and effective, M72/AS01E could potentially 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.

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.

The Gates MRI, a nonprofit organization and subsidiary of the Bill & Melinda Gates Foundation, is sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome. GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the vaccine for the Phase 3 trial and will provide the adjuvant post licensure should the trial be successful. An adjuvant is an ingredient used in some vaccines that can help create a stronger immune response.

 Previous Development of the M72/AS01E TB Vaccine Candidate: 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 Bill & Melinda Gates Foundation. In 2020, GSK announced a partnership with the Gates MRI for further development of M72/AS01E.

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, which was unprecedented in decades of TB vaccine research. The World Health Organization estimates that over a 25-year time span, that level of protection could save 8.5 million lives, prevent 76 million new TB cases and save $41.5 billion for TB affected households.