Tuberculosis

The End TB strategy aims for a 90% reduction in deaths and an 80% drop in incidence by 2030. New diagnostics, drugs, and vaccines are vital to achieve this.

As of December 2023, at least 114 different TB counter measures are in development. Anti-tubercular drugs, including regimens, make up nearly half of the pipeline, diagnostics account for just under a third, and the remaining pipeline comprises vaccines (18%) and biologics (4%).

The pipeline includes novel and safer drugs that will help shorten treatment and diverse diagnostics that will help replace sputum smear microscopy as the initial test. Vaccines require an urgent influx to the pipeline to make delivery of the next-generation TB vaccine a reality.

Safer, shorter pan-TB regimens

The pipeline of new chemical entities (NCEs) in clinical development has increased more than three times since 2015. The front-running candidates include quabodepistat, which is being investigated as part of a regimen for shortening DS-TB treatment from six months to two to four months. The interim analysis from an ongoing clinical trial showed a high cure rate among participants taking quabodepistat-based regimens.

Next-generation TB vaccine: preventing infection and disease among all age groups

BCG, the only licensed TB vaccine available, is ineffective among adolescents and adults which are the age groups with the highest burden. The lack of a next-generation TB vaccine with the ability to prevent all forms of TB, including infection and disease, among all age groups is the biggest obstacle to achieving the goals set in the End TB Strategy.

But vaccine development has seen dismal progress, with numerous unsuccessful clinical trials. M72/AS01E-4 is the only investigational vaccine to successfully complete a phase IIb efficacy trial. A phase 3 clinical trial is now underway. The first-ever mRNA-based vaccine has recently started a phase I trial. More early-stage research, potentially translating into a more diverse clinical pipeline, is urgently needed.

Diagnostics remain the weakest link in the TB cascade of care but the pipeline has diversified at a fast pace

In 2022, close to 30% of people with TB were never diagnosed and therefore left untreated. New tools appropriate for resource-limited settings for screening, diagnosing and monitoring treatment response are critical to reap the benefits of newer and shorter treatments.

The diagnostics pipeline has decreased since 2015 but in terms of diversity of use-case, the current pipeline is the healthiest it has ever been. Almost 60% of the tests currently in development are based on molecular platforms, and all but one of the remaining are immunoassays. Confirmatory tests with the ability to test drug resistance make up 29% of the pipeline, followed by POC diagnosis (26%), triage and screening tests (21%) and treatment monitoring (12%).

“Yes, We Can End TB”, if we uphold the remarkable research strides witnessed in therapeutics and diagnostics over recent years, coupled with a coordinated global effort to expand the vaccine pipeline

After years of neglect with no significant results, the pipeline shows signs of improvement. The current drug pipeline is expected to deliver shorter, easy-to-administer TB treatment in the next five years. The diagnostics pipeline has diversified at a fast pace, and it now seems possible that sputum smear microscopy will be wholly replaced with POC molecular tests in the near future.

Vaccine research is one area that needs urgent attention. More pre-clinical candidates with diverse antigen profiles are required to bolster and replenish the pipeline. The establishment of the TB Vaccine Accelerator Council by the WHO is a step in the right direction.