In March 2024 The Bill & Melinda Gates Medical Research Institute (Gates MRI) announced the commencement of a Phase III clinical trial to assess the efficacy of the M72/AS01E tuberculosis (TB) vaccine candidate. The first doses will be administered in South Africa, where the disease “takes a heavy toll”. Gates MRI states that, if the vaccine is well-tolerated and effective it could potentially become the first vaccine to help prevent pulmonary TB in adolescents and adults and the first new TB vaccine in over a century.
The burden of TB
WHO estimates that 10.6 million people became ill with TB in 2022, with 1.3 million deaths: over 3,500 people died each day. The disease “primarily affects people in low- and middle-income countries”, with the people at highest risk “often living in poverty”. Gates MRI states that, in South Africa alone, around 280,000 people are diagnosed with TB each year. TB is “one of the world’s deadliest infectious diseases” and the “leading cause of death amongst people living with HIV”. However, the only available vaccine, BCG, was developed in 1921 and offers “inadequate protection” to adolescents and adults against the pulmonary form of the disease.
Dr Emilio A. Emini, CEO of Gates MRI, commented that the launch of the trial “demonstrates our commitment to harnessing the power of medical innovation to fight diseases like TB”. These diseases are “particularly devastating for low- and middle-income countries”.
“Clinical study of the vaccine will still require years, but our incredible partners in South Africa and elsewhere who have come together for the Phase III study share our hope in the vaccine’s potential.”
Dr Lee Fairlie, Director of Maternal and Child Health at Wits RHI at University of the Witwatersrand in South Africa, and national principal investigator for South Africa, emphasises that this trial is an “important moment for South Africans” that demonstrates “a strong local and global commitment to fight a disease that remains distressingly common in our communities”.
“South Africa also has considerable experience with TB- and vaccine-related clinical trials and a strong track record for protecting patient safety and generating high quality data essential for regulatory approvals.”
Getting the vaccine to trial
The M72/AS01E vaccine candidate has been in development “since the early 2000s”, originally designed and clinically evaluated by GSK in partnership with Aeras and IAVI. In 2020, GSK announced a partnership with Gates MRI to further develop the vaccine. GSK “continues to provide technical assistance” and supplies the adjuvant component of the vaccine. GSK will provide the adjuvant post licensure if the trial is successful. The trial is sponsored by Gates MRI, with funding from the Gates Foundation and Wellcome.
Gates MRI, GSK, Wellcome, and the Gates Foundation are working together to understand the potential demand for the vaccine and develop an end-to-end plan that ensures long-term sustainable access if the trial is successful. This involves supporting research and building an evidence-base for the potential effect of the vaccine and community requirements for uptake as well as collaborating with multilateral, regional, and country partners to introduce the vaccine. The trial funders also intend to form an international advisory group comprising representatives of these groups to provide input on the programme.
The trial is expected to include up to 20,000 participants, including people living with HIV, across up to 60 trial sites in seven countries: South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia, and Vietnam. Participants will either receive the investigational M72/AS01E vaccine or placebo in the double-blind trial. The trial is anticipated to last up to 5 years before data analysis and preparation for submission to regulatory authorities.
Deborah Waterhouse, CEO, ViiV Healthcare, and President, Global Health, GSK, is “delighted” that the trial is underway after GSK has dedicated “over 20 years to developing this essential candidate vaccine”.
“Developing and ensuring access to global health products is complex but our collaboration with the Gates MRI, Wellcome, and the Gates Foundation exemplifies the transformative power of leveraging disease partners’ expertise to change the trajectory of challenging diseases, like TB, which place a huge burden on communities around the world.”
Dr Alemnew Dagnew leads the development of the vaccine at Gates MRI and is “particularly excited to see this trial get underway” after experience working as a physician in Ethiopia, which revealed the effect of pulmonary TB on communities.
“If effective M72/AS01E could reinvigorate a global fight against TB that has been weakened by the COVID-19 pandemic.”
Dr Dagnew commented that TB represents both a health and a socioeconomic problem, with the disease primarily affecting people in their “prime” working years, leaving families without income and children without parents. Almost half of TB-affected households face costs higher than 20% of their household income. Dr Trevor Mundel, President, Global Health, Gates Foundation, echoed that the start of the trial is a “pivotal moment” in the fight to “end TB, which devastatingly afflicts the world’s most vulnerable communities”.
“We think this trial marks the beginning of a series of opportunities that will usher in the most promising pipeline ever of new TB tools.”
Dr Mundel stated that the Gates Foundation “remains committed to supporting local and global partners to accelerate the solutions needed to save lives and reduce suffering”. Dr Alex Pym, Wellcome’s Director of Infectious Disease, recognised that there is a “long journey to results”. However, the start of the trial “brings us a critical step closer to having an effective vaccine to protect those most at risk of TB”.
“Global collaboration with regulators, in-country decision makers, and communities affected is crucial if those who need it most are to benefit from this vaccine, should the trial be successful.”
To connect with representatives from some of the organisations behind this trial, such as Gates MRI, Wellcome, and GSK, join us in Washington for the Congress this April. Don’t forget to subscribe for further insights into vaccine trials and development.
