A Phase 3 trial for the tuberculosis vaccine known as M72/AS01E is running a year ahead of schedule and has already recruited 90% of the 20,000 people it needs, according to Dr Alemnew Dagnew, who leads its clinical development.

The vaccine aims to prevent adolescents and adults already infected with latent TB from developing pulmonary TB. In countries with high TB burden, vast numbers of people have latent TB, which means that they are infected with the TB bacteria but not symptomatic or infectious. People with latent TB do not generally develop TB disease unless their immune systems are compromised.

The trial scientists initially thought it would take two years to recruit all the study participants at the 54 trial sites spread across South Africa, Kenya, Zambia, Malawi and Indonesia.

“We started the trial last year in March, and we have already enrolled more than 90% of the participants, which is huge progress, and we are hoping to have full enrollment in the coming weeks,” Alemnew told Health Policy Watch this week. “It’s one year ahead of our projection.”

Alemnew works for the Gates Medical Research Institute (Gates MRI), which is sponsoring the trial, while funding comes from the Gates Foundation and Wellcome Trust.

The sites were chosen because they are in communities where there is a high TB incidence and because of the countries’ capability to conduct clinical research, said Alemnew.

Efficacy of 50% in Phase 2b trial

A Phase 2b trial of the vaccine found that it was 50% effective in blocking latent TB from becoming pulmonary TB. This would not have been efficacious enough to persist with a costly Phase 3 trial for many other diseases. But because of the enormous global burden of TB, 50% efficacy will save millions of lives.

“If we think about the population level, the impact is going to be huge,” said Alemnew.

“If I can throw in some numbers, the World Health Organisation (WHO) estimates that, over 25 years, a vaccine with 50% efficacy for protecting adolescents and adults could save 8.5 million lives, prevent 76 million new TB cases and save $41.5 billion for TB-affected households.”

Currently, the only available TB vaccine is BCG, which is given to newborn babies. It was first administered to humans in 1921 and no new vaccines have been developed despite TB being one of the world’s most deadly infectious diseases.

While the BCG vaccine “works well in preventing severe forms of childhood TB, its efficacy against prevention of preliminary TB in adolescents and adults is insignificant,” notes Alemnew.

Of the 20,000 participants – aged from 15 to 44 – 18,000 will be infected with TB, 1000 participants will be non-TB infected and 1000 will be people living with HIV.

The trial will stop once 110 people have developed pulmonary TB, he adds – by which time scientists enough data will have been generated to analyse the vaccine’s efficacy.

Tech transfer

First developed by GSK, the M72/AS01E vaccine is made up of a fusion of two TB antigens combined with an adjuvant (AS0) to boost the body’s immune response.

Trial participants will get two doses of the vaccine or a placebo 28 days’ apart, with telephonic follow-up every two months and a clinic visit every six months until the trial is over.

GSK developed the vaccine over many years, and published the results of its Phase 2b results in the New England Journal of Medicine (NEJM) in 2018 and 2019. Gates MRI then stepped in to license the vaccine candidate.

“GSK continues to provide the adjuvant component for clinical trials, and will also for the commercial product [if the Phase 3 trial is successful]. They have also been working with us to have technology transfer to manufacture the antigen component,” said Alemnew.

Personal mission

Alemnew was born and raised in Ethiopia, where he also trained as a physician and practised medicine.

“One of the most one of the common health conditions that I used to manage was TB, so have seen the devastating impact of TB on patients, their families and also the communities,” he said.

“TB affects people of poor socio-economic status. If a family member gets sick with TB, then they would have to stop working. If that family member is the only source of income, the whole family will be in a bad situation. 

“Developing a vaccine like the one which I’m currently working on, [if successful] is going to be like a gift to the community that I came from.

 “So for me, it’s a great honour and privilege to work on this important vaccine. It’s going to motivate not only those of us who are working on this vaccine, but the whole TB research community.”

Image Credits: Socios en Salud , Bryce Vickmark.