An investigational three-drug regimen that could cut tuberculosis (TB) treatment from six months to four is now in a phase 3 clinical trial, arriving as the World Health Organization (WHO) reports an estimated 10.7 million people fell ill with TB in 2024 and approximately 1.23 million died from the disease, with drug-resistant TB continuing to spread worldwide. The trial pairs a novel compound, OPC-167832, with two newer anti-TB drugs in what researchers hope will be a faster, better-tolerated option, even as only about two in five people with drug-resistant TB currently access treatment worldwide.
Global TB Burden Keeps Climbing Despite Partial Progress
The WHO’s Global Tuberculosis Report 2025, drawing on surveillance from 184 countries, presents a mixed picture of progress and setback. According to the latest global estimates, 10.7 million people developed TB in 2024 and roughly 1.23 million died, including deaths among people living with HIV. While reported case notifications have rebounded from the disruptions of the COVID-19 pandemic, the sheer scale of illness underscores that TB remains one of the world’s deadliest infectious diseases. Some 8.3 million people were newly diagnosed and started on treatment in 2024, a record figure, yet millions more were missed by health systems and continued to transmit the infection in their communities.
The burden falls disproportionately on low- and middle-income countries, where health systems face chronic resource constraints. In the WHO African Region, for example, TB services must compete with other pressing priorities such as malaria, HIV, and maternal health, stretching limited budgets and staff. Regional offices like WHO Africa have emphasized that TB control depends not only on better drugs but also on stable funding for laboratories, community health workers, and preventive care. Without sustained investment in those building blocks, even the most advanced regimens risk reaching patients too slowly to reverse entrenched transmission patterns.
Drug-Resistant TB Exposes Gaps in Access and Control
The drug-resistant side of the epidemic is especially alarming. WHO trend data on multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB) from 2015 to 2024 show that global incidence has not been brought under control, with resistant strains continuing to emerge and spread. Rifampicin, a cornerstone of standard TB therapy, is losing its effectiveness in many settings, forcing clinicians to rely on more complex, expensive, and toxic regimens. These second-line treatments often require longer durations, close monitoring, and specialized expertise that are not readily available in many high-burden countries.
Access to treatment for drug-resistant TB remains deeply inequitable. According to the WHO’s TB fact sheet, only about two in five people with MDR/RR-TB actually receive appropriate therapy, leaving the majority without effective drugs. That treatment gap fuels ongoing transmission, entrenches resistance, and contributes to preventable deaths, particularly in regions already battling constrained health budgets. It also highlights why innovation in regimen design, shorter, safer, and easier-to-deliver combinations, is seen as critical to bending the drug-resistant curve, rather than relying solely on incremental improvements to existing six-month protocols.
A Shortened Regimen Enters Phase 3 Testing
Against this backdrop, a pivotal phase 3 trial is testing whether a four-month regimen built around the novel compound OPC-167832 can rival the current standard of care. The study, registered as NCT05221502, uses an open-label, randomized design to compare OPC-167832 plus delamanid and bedaquiline against the standard six-month regimen for drug-susceptible pulmonary TB. OPC-167832, developed by Otsuka Pharmaceutical, belongs to a new antibiotic class targeting the mycobacterial cell via a mechanism distinct from first-line drugs like isoniazid and rifampicin. This raises hopes that it can help overcome existing resistance patterns while maintaining potent bactericidal activity.
The trial’s primary question is whether four months of therapy can achieve non-inferior cure and relapse rates compared with six months, while also offering a more favorable safety and tolerability profile. If successful, the regimen could significantly reduce the time patients must remain on daily treatment, a factor closely linked to adherence and outcomes. Shorter courses reduce the window for missed doses and treatment interruptions, which are key drivers of resistance. They could also lower costs for health systems by decreasing clinic visits, laboratory monitoring, and the logistical burden of drug supply, especially in high-burden countries that struggle to maintain uninterrupted access to existing medicines.
Next-Generation Drugs Aim to Cut Toxicity and Time
The OPC-167832 regimen is part of a broader wave of research rethinking how TB is treated, with a particular focus on reducing toxicity and duration. A phase 2b dose-finding study known as PanACEA-DECODE-01, reported in The Lancet Infectious Diseases, evaluated delpazolid, a next-generation oxazolidinone, in combination with bedaquiline, delamanid, and moxifloxacin. Delpazolid was engineered to retain the potent anti-mycobacterial activity of linezolid while mitigating severe side effects such as bone marrow suppression and peripheral neuropathy that often limit linezolid’s use in longer regimens. The randomized, open-label trial assessed early bactericidal activity and culture conversion, providing key data to refine dosing strategies that balance efficacy with safety in multidrug combinations.
Other experimental regimens push the boundaries of how short TB treatment might become. Phase 2 results released in November 2025 suggested that, under carefully controlled conditions, it may be possible to shorten therapy to as little as one month, though such ultra-short courses will require extensive validation in larger, diverse populations before they can be widely adopted. In parallel, an economic evaluation from the London School of Hygiene and Tropical Medicine identified a newly recommended regimen for rifampicin-resistant TB as the most cost-effective option currently available, underscoring that advances in pharmacology must be matched by affordability and accessibility to have real-world impact. Together, these studies point toward a future in which TB treatment is not only shorter but also better tailored to patients’ needs and health system realities.
From Clinical Trials to Real-World Impact
Bringing these innovations from trial registries and journal pages into clinics will hinge on coordinated global action. Regulatory authorities will need to review emerging phase 3 data quickly but rigorously, while WHO and national TB programs translate evidence into updated guidelines and procurement plans. High-burden countries will face decisions about how to phase in new regimens alongside existing ones, manage training for frontline health workers, and ensure that diagnostic capacity keeps pace so that patients are matched with the right treatment from the outset. Without robust systems to track outcomes and safety, even the most promising regimen could falter when scaled up.
At the same time, the success of shorter, next-generation regimens will depend on sustained financing and political commitment. Donor agencies, multilateral funds, and domestic governments will have to weigh the upfront costs of adopting new drugs against the longer-term savings from fewer hospitalizations, reduced transmission, and averted deaths. Communities affected by TB, including people with drug-resistant disease and those living with HIV, are increasingly vocal in calling for access to cutting-edge therapies rather than being left with outdated, toxic options. As the OPC-167832 combination and other regimens progress through late-stage testing, the central challenge will be ensuring that scientific progress translates into tangible gains for the millions still at risk of falling ill with TB each year.
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*This article was researched with the help of AI, with human editors creating the final content.
