There have been widespread reports that more effort and funding is needed to combat the TB crisis. As more cases of Sirturo (bedaquiline) resistance have been reported, it is vital that more therapies are available to target multi-drug resistant tuberculosis (TB).
Today marks World TB Day, which is observed annually on March 24 and amplifies the urgency of ending TB. This year’s theme is “Yes! We Can End TB: Commit, Invest, Deliver” – a bold call for hope, urgency, and accountability.
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While the World Health Organization (WHO) has put out an urgent call for more funding for research as it tries to reach the End TB 2030 target, the clinical space is still relatively lacking.
Director of WHO’s Global Programme on TB and Lung Health, Dr. Tereza Kasaeva said: “This urgent call is timely and underscores the necessity of swift, decisive action to sustain global TB progress and prevent setbacks that could cost lives. Investing in ending TB is not only a moral imperative but also an economic necessity—every dollar spent on prevention and treatment yields an estimated $43 in economic returns.”
TB has recently taken its spot again as the world’s top infectious killer, with Covid-19 topping the list in recent years. TB is caused by the bacteria mycobacterium TB and impacts the lungs. Every year, 10 million people fall ill with TB and despite being a preventable and curable disease, 1.5 million people die from TB each year. TB is the leading cause of death of people with human immunodeficiency virus (HIV) and a major contributor to antimicrobial resistance (AMR).
The treatment landscape for drug-resistant TB was relatively barren until the approval of Johnson & Johnson’s Sirturo. The therapy was granted accelerated approval by the US Food and Drug Administration (FDA) in December 2012 and conditional approval from the European Medicines Agency (EMA) in 2014 to treat multi-drug-resistant TB. It received full approval from both agencies back in 2024.
Despite it only having been available beyond clinical trials for just over a decade, there is already resistance to this therapy being reported. Resistance to the adenosine triphosphate (ATP) synthase inhibitor, has been noted in South Africa, Mozambique, Eswatini and provinces of China including Zhejiang, as well as other low- and middle-income countries where disease prevalence is higher.
Experts are emphasising that it is critical for more therapies to be investigated to tackle an issue which will only worsen over time.
How does the research space look?
According to GlobalData’s Pharmaceutical Intelligence Centre, there are 308 clinical trials investigating therapies for TB, pulmonary TB and mycobacterium TB infections that are ongoing or planned.
GlobalData is the parent company of Pharmaceutical Technology.
Concern over Sirturo resistance is already noted among experts, with GlobalData infectious disease analyst Stephanie Kurdach saying that key opinion leaders (KOL) have shared their concerns. Kurdach said that one KOL spoke about his concern about physicians using Sirturo for nontuberculous mycobacteria, an indication that the therapy is currently being investigated.
The KOL said that while it is positive that this therapy is being investigated in nontuberculous mycobacteria, they shared concerns about how its use in these patients might impact the future treatment of multi-drug resistant TB.
Paul Sommerfeld, executive trustee of TB Alert and member of the community advisory body of UNITE4TB, says that programmes using Sirturo are being strict about its usage due to these concerns.
“Almost any drug you use is going eventually to have resistance developed against it. Programmes that are using it are being urged to be very strict about how they use it to try and minimise the development of resistance,” Sommerfeld says.
“We need a constant stream of new drugs for a disease like TB because resistance is always going to happen. Recently, there have been quite a few new drugs that have come to the forefront and are just being investigated which will be helpful in future, but the actual pipeline of yet further possible drugs is rather thin, and we need further research to help with that.”
The UNITE4TB programme, which has been established in Europe, aims to set a new standard for anti-TB regimen development by upgrading the current clinical trial methodology and enhancing the efficiency with which new regimens are delivered.
The clinical trial programme was launched at the end of 2023 with the PARADIGM4TB (NCT06114628) and DECISION (NCT05926466) trials, evaluating combination therapies for TB treatment. Since this, the Phase II ENABLE study (NCT06748937) has also been initiated, evaluating the efficacy of BioVersys and GlaxoSmithKline’s (GSK’s) alpibectir plus ethionamide combination.
Other studies are being conducted globally, investigating various novel approaches for both treatment and prevention.
“We hope that with those, we will be able to hold the problems of resistance at bay, and secondly, that we will bring the length of time of treatment down. Now, somebody with TB who is not resistant is being treated for six months, and that’s a lot of pills in a long period of time,” Sommerfeld explains. “So, we are hopeful that fairly quickly, we will have regimens which will bring us down at least to a four-month time period, and preferably two or three months. While it doesn’t seem impossible, we are a few years away from that yet.”
Funding about to take a bigger hit
While funding for the disease has already been low for decades, this is set to be exaggerated by the US withdrawing from the WHO and pulling United States Agency for International Development (USAID) funding.
The WHO said it has already received early reports of severe disruptions in the TB response across several of the highest-burden countries following the funding cuts. Countries in the WHO African Region are experiencing the greatest impact, followed by countries in the WHO South-East Asian and Western Pacific Regions.
The 2025 funding cuts further exacerbate an already existing underfunding for global TB response. In 2023, only 26% of the $22bn annually needed for TB prevention and care was available, the WHO says. The organization adds that the TB research space is also in crisis, receiving just one-fifth of the $5bn annual target in 2022, delaying advancements in diagnostics, treatments, and vaccines.
Sommerfeld adds: “There’s a there’s a fear that with less US money available, quite a lot of research will be slowed down or will not be able to happen. We’ve never got to a stage of having as much funding as we think would be necessary. We’ve always been working kind of hand to mouth.”
Not all hope is lost
While this paints a rather bleak picture of the TB space, there have been advancements that give experts reason for optimism in the sector.
Sommerfield concludes: “In a way, we are at a period of optimism in terms of TB. We do have this new regimen and we have new ideas for how to prevent TB developing in a person, but we always face this problem of resistance, and we desperately need to keep going with as much research as possible on alternative regimens.”
With more therapies in trials, there is a hope that a more effective treatment regimen will be available to patients across the world, but much of that relies on people responding to the End TB 2030 call.
