Neglected Diseases
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an airborne disease that most commonly affects the lungs, and is the leading cause of death of any single infectious pathogen.
Almost a quarter of the world’s population is estimated to be infected, but most TB cases are latent and non-infectious; around 5-15% will progress to active TB if left untreated. Active TB usually causes a chronic cough, fever and weight loss. TB is especially dangerous for people with low immunity, and is a leading cause of death among people with HIV/AIDS. There is also growing resistance to existing treatments.
A new TB vaccine, which is effective across all ages and safe for pregnant and lactating women, is critical for achieving targets set by the WHO’s End TB Strategy. However, TB vaccine R&D is lagging on most fronts – the number of candidates in late clinical development is unchanged, and most are non-inactivated/attenuated vaccines targeting the same antigen, no new evidence on efficacy since the publication of M72/AS01E’s clinical trial results in 2019 and the exclusion of pregnant women, a high-risk group, from clinical trials. A more diverse early-stage pipeline is urgently needed to safeguard against the potential failure of the current clinical candidates. In recent years, the WHO has endorsed several new tools, including molecular tests for diagnosing TB. However, research gaps still exist, including non-sputum-based tests for diagnosing paediatric TB, true point-of-care molecular tests and tools for screening and triage.
After more than five years without any new vaccine candidates entering clinical development, in 2023 two new TB vaccines were slated to enter clinical trials: BioNTech’s mRNA TB vaccine, a first of its kind, began its Phase I trial in July 2023; and Statens Serum Institut’s H107e/CAF 10b, an adjuvanted subunit vaccine, is expected to start recruiting participants by late 2023. Similarly, after more than five years since we last saw a positive result from a Phase II vaccine trial, the Gates MRI are set to begin Phase III trials of the M72/AS01E vaccine candidate in early 2024. Results from the SUDOCU Phase IIb drug trial demonstrated that in different doses, sutezolid is a safe addition to bedaquiline, delamanid, and moxifloxacin regimen for treating DS-TB. In 2023, the WHO recommended a new class of tests: targeted next-generation sequencing (NGS) for detecting drugresistant TB. At least one NGS technology, DeepChek DST, is undergoing WHO review.