Posted on: Thu 21-03-2024

The Bill & Melinda Gates Medical Research Institute (Gates MRI) has commenced a phase III clinical trial to assess the efficacy of the M72/AS01E tuberculosis (TB) vaccine candidates with first doses in South Africa.

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.

A large Phase III trial will evaluate whether the M72/AS01E vaccine candidate can protect adolescents and adults from pulmonary tuberculosis. The Clinical trial site at the University of the Witwatersrand, Johannesburg, South Africa, is the first of up to 60

sites in seven countries. The M72/ASO01E vaccine candidate could be the first new TB vaccine in 100 years if proven effective.

According to the World Health Organisation (WHO), an estimated 10.6 million people fell ill globally with TB in 2022 and 1.3 million died representing over 3,500 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. In South Africa alone, around 280,000 people are diagnosed with TB each year.

Commenting on the development, the CEO of the Gates MRI, Emilio Emini, noted that the launch of the pivotal Phase ITI trial demonstrates the institute's commitment to harnessing the power of medical innovation to fight diseases like TB that are particularly devastating for low- and low-middle-income countries.

He observed that the “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.”

According to a statement, the Gates MRI, a nonprofit organisation and subsidiary of the Bill & Melinda Gates Foundation, is sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome.

It added that the M72/ASO0iE vaccine candidate has been in development since the early 2000s and 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) was funded by GSK and in part by the Gates Foundation.

“In 2020, GSK announced a partnership with the Gates MRI for further development of M72/AS01E. GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the vaccine for the Phase ITI 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.”

The institute further noted that making vaccines accessible and affordable for communities in areas of high disease burden in the long term is a priority for all trial partners adding that the Gates MRI has worked with a wide range of stakeholders, including communities around clinical trial sites, to guide the TB candidate vaccine to Phase III.

“To this end, the Gates MRI, GSK, Wellcome and the Gates Foundation are working together to understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term sustainable access, should the trial be successful; from supporting research and building an evidence-base for the potential impact of the vaccine and community requirements for uptake, to collaborating with multilateral, regional and country partners required to introduce the vaccine. Additionally, the trial funders are planning to establish an international advisory group comprised of representatives from all these groups to provide input on the overall programme.

“Reaching Phase III with an urgently needed TB vaccine candidate is an important moment for South Africans because it demonstrates that there is a strong local and global commitment to fight a disease that remains distressingly common in our communities,” said Dr Lee Fairlie, Director of Maternal and Child Health at Wits RHI at University of the Witwatersrand, Johannesburg, South Africa, and national principal! investigator for the trial in South Africa.

“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.”

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 the vaccine or placebo. This approach is considered the gold standard for evaluating the safety and efficacy of an investigational vaccine.

“Also, the CEO, of ViiV Healthcare and President, of Global Health, GSK, Deborah Waterhouse said, “After dedicating over 20 years to developing this essential candidate vaccine, we at GSK are delighted that the Phase III trial is underway. 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 diverse partners’ expertise to change the trajectory of challenging diseases, like TB, which place a huge burden on communities around the world.”

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 the transmission of the TB bacterium.

“If effective, M72/AS01E could reinvigorate a global fight against TB that has been weakened by the COVID-19 pandemic,” said Alemnew Dagnew, M.D., who leads the development of M72/AS01E at the Gates MRI. “I am particularly excited to see this trial get underway because when I was working as a physician in Ethiopia, I saw first-hand what pulmonary TB does to communities — and a vaccine that could help prevent that from happening would be transformative.”

Dagnew noted that TB is both a health problem and a socioeconomic problem. He said the disease primarily affects people during their prime working years, leaving families without income and children without parents. Almost half of TB-affected households face costs higher than 20 per cent of their household income.

“We must continue to move with urgency to develop and equitably deliver innovative tools with the potential to transform the prevention, diagnosis, and treatment of TB. The start of the Gates MRI’s M72 TB vaccine candidate Phase III clinical trial marks 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,” Dagnew added.

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