How is tuberculosis vaccine and treatment research progressing?


March 24, 2023

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helio interview

Disclosure:
Beumont and Cohn do not report related financial disclosures.


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Important points:

  • Currently, the tuberculosis treatment pipeline is the largest ever.
  • These are 24 tuberculosis vaccine candidates being evaluated in 29 studies.

During the COVID-19 pandemic, World Tuberculosis Day on 23 March each year highlights the need for more research, more testing, more treatment options, and more access to patients around the world. is showing.

Luckily, we need more this year, David L. Cohn, M.D., infectious disease news The editorial board member and professor of medicine at the University of Colorado School of Medicine’s Division of Infectious Diseases said both tuberculosis treatment and vaccine research, which has been hampered in many parts of the world, are gaining momentum.

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Helio talks to Korn, Maria Beaumont, MD, TB Alliance Vice President and Chief Medical Officer on the current state of TB treatment and vaccine research and what progress has been made after the disruption caused by the COVID-19 pandemic that has had a major impact on the fight against TB. I gave my opinion.

Helio: After being interrupted by the COVID-19 pandemic, is tuberculosis vaccine and treatment research back on track?

Beaumont: Although there have been many important advances in the treatment of drug-resistant tuberculosis in recent years, statistics have largely remained stagnant due to the recent increase in mortality from COVID-19.

Each year, 10 million people contract tuberculosis, and 1.6 million will die in 2021 alone. Global funding levels are well below those needed to control the tuberculosis pandemic. It is the resources, funding and global commitment to safeguarding global health that will continue to advance the science of developing life-saving tools and treatments.

corn: For the most part, both tuberculosis treatment and vaccine research picked up pace after being severely hampered in many sites and countries in terms of enrollment and retention of participants and the personnel available to conduct research. Some units have devoted resources to COVID-19 research and management. Others simply slowed down or shut down.

That said, many plans for drug development and clinical protocols continued, albeit via conference calls and virtual meetings. A remarkable example of resilience during the pandemic is worth noting. The recently published TRUNCATE-TB trial enrolled 675 participants at 18 sites in 5 countries in Asia and Africa from March 2018 to January 2020 (pre-pandemic) and will continue through December 2021. was able to achieve 99% follow-up at 96 weeks (pandemic).

Helio: What’s in the pipeline for new treatments for tuberculosis?

Beaumont: We currently have the largest pipeline of new TB medicines in history and are working with partners to advance compounds and medicines through all stages of clinical development. We recently announced terasevec, a new compound licensed by the Tuberculosis Alliance from South Korea-based Client to continue its development as an anti-tuberculosis drug.

corn: A major focus of TB treatment trials over the last decade has been the use of new combinations of licensed anti-TB drugs to treat both drug-susceptible (DS-TB) and drug-resistant (MDR-, XDR-TB) TB. was to shorten the treatment of At or higher doses, in combination with the newer drugs bedaquiline and pretomanide, and linezolid, one drug not originally developed for tuberculosis.

Despite several failures with regimens of less than 6 months for DS-TB and 18-24 months for MDR-TB (in the last 40 years), great progress has been made in the last 2 years.

These success stories include positive results in terms of:

A tBTC31/ACTG5349 study with rifapentine, moxifloxacin, isoniazid and pyrazinamide administered for 17 weeks for DS-TB.

NIX-TB and XeNIX studies with bedaquiline, pretomanide, and linezolid for 26 weeks for MDR- and XDR-TB;t

The SHINE trial of non-severe pediatric tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol for 16 weeks.and

A TRUNCATE-TB study with bedaquiline, linezolid, isoniazid, pyrazinamide, and ethambutol administered for 8 weeks. Other treatment-shortening trials with various combinations of drugs are due to be completed this year, and some have begun enrollment or are in the planning stages.

In terms of new drugs in the pipeline, the latest report from the Stop TB Partnership’s working group on new TB drugs found 31 new compounds from 12 different drug classes with different mechanisms of action, 13 of which are in preclinical development. indicates that it is in , 6 in a phase 1 trial and 12 in a phase 2 trial.

Examples of drugs in Phase 2 trials include stezolide (SUDOCU trial) and delpazolide (DECODE trial). These are investigational oxazolidinones that may be less toxic than linezolid and frequently cause dose-dependent peripheral neuropathy and myelosuppression.

Amid the pandemic, a new tuberculosis clinical trial group has emerged. There are currently 11 groups funded by governments, academic centers, the Bill and Melinda Gates Foundation, and at least he has six pharmaceutical companies involved.

Therefore, safer, more effective, and shorter-term dosing regimens are expected in the future.

Helio: What’s in the tuberculosis vaccine pipeline?

Beaumont: In addition to new treatments, new and improved tuberculosis vaccines are a priority for the global health community. The existing vaccine, the Bacillus Calmette-Guérin (BCG) vaccine, is over 100 years old and only partially effective. The BCG vaccine is used primarily to prevent the most serious form of tuberculosis in children.

corn: Based on the TB Vaccine Initiative’s 2022 TB Vaccine Pipeline Grid, there are 24 vaccine candidates in 29 studies, 8 of which are preclinical, 6 in phase 1, 4 in phase 2a, 5 in phase 2b, and 6 in phase is 3. Includes adjuvanted protein subunit vaccines, live attenuated strains, inactivated whole-cell mycobacterial and viral vector vaccines. There are 3 studies in infants and neonates, 18 studies in adolescents and adults, and 8 therapeutic studies.

In phase 2b trials in South Africa, Kenya and Zambia, the GSK M72/AS01E vaccine (subunit containing adjuvant) showed promise, showing 54% efficacy in preventing pulmonary tuberculosis. M.tb– Infected (IGRA-positive) adolescents and young adults and persistent immunogenicity after 3 years. GSK has turned over the vaccine to the Gates Medical Research Institute (MRI) for further development and potential Phase 3 trials in a larger and more diverse patient population.

Before embarking on an expensive and potentially definitive phase III trial, Gates MRI was conducting a large-scale epidemiological study of tuberculosis incidence at 50 sites in 14 high-burden countries. We are enrolling 8,000 participants aged 15 to 34 for proper planning. Sample size, duration, and cost using site-specific data.

Another notable candidate is VPM1002, a recombinant BCG vaccine. In a phase 2b trial in infants, VPM1002 was less reactogenic and immunogenic than BCG, less lymphadenopathy and scarring, lower interferon gamma levels, and lower multifunctional CD4 and CD8 cells . The Serum Institute of India is conducting a Phase 3 double-blind trial comparing VPM1002 with BCG, enrolling 6940 newborns aged <14 days in 5 African countries. Endpoints are quantum ferron conversion and incidence of tuberculosis disease at 12-36 months of age.

Finally, the impressive results of messenger RNA vaccines for preventing COVID-19-related hospitalizations and deaths have raised the question of whether this platform can be used for the development of new tuberculosis vaccines. Preliminary work has been done and there are some data suggesting which protein antigens can be generated with RNA technology and are sufficient to generate an effective vaccine immune response. There is room for optimism, but it is too early to judge.

Helio: Realistically, how quickly does the world better tuberculosis vaccine ?

corn: Despite these advances and great potential, it will still take many years to develop, accept and license a safe and effective alternative to the more than 100-year-old BCG vaccine.



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