WHO Recommends MSF-Led EndTB Clinical Trial Treatments for Multidrug-Resistant Tuberculosis
The World Health Organization (WHO) has recently made a groundbreaking announcement by recommending three new treatment regimens for multidrug-resistant tuberculosis (MDR-TB). These regimens were developed based on the results of the EndTB clinical trial, a multi-year study led by Doctors Without Borders/Médecins Sans Frontières (MSF). This initiative aimed to find more tolerable and effective drug options for TB patients. The significance of these new regimens lies in their all-oral composition and much shorter treatment duration of nine months compared to the traditional 18-month regimen. This advancement is particularly crucial as it offers a more manageable and less burdensome treatment path for patients suffering from MDR-TB.
The EndTB clinical trial, which spanned from 2017 to 2023, was conducted in collaboration with Partners in Health (PIH) and Interactive Research and Development (IRD), with funding from Unitaid. The primary objective was to identify shorter, more tolerable, and injection-free treatments for MDR-TB using combinations of newly developed drugs like bedaquiline and delamanid. These two drugs represent significant breakthroughs as they are the first new TB drugs developed in nearly 50 years. The pharmaceutical industry’s reluctance to invest in TB research, primarily because the disease predominantly affects poorer communities, underscores the importance of independent actors like MSF in spearheading such initiatives.
Dr. Lorenzo Guglielmetti, the director of the EndTB project at MSF, hailed the WHO’s recommendations as a major step forward for the health of millions of patients affected by MDR-TB. The EndTB regimens have been found to be at least as effective as conventional treatments for patients with multidrug-/rifampicin-resistant TB (MDR-/RR-TB). This is a significant achievement considering that MDR-TB is resistant to the two most powerful first-line antibiotics, rifampicin and isoniazid, making it particularly challenging to treat. The easier and shorter treatment options provided by the new regimens are expected to encourage better adherence to treatment protocols, which is critical for the effective management of infectious diseases like TB.
The WHO’s endorsement of these new regimens is based on comprehensive evidence gathered from the EndTB clinical trial and another MSF-led trial called TB Practecal. Both trials have demonstrated the efficacy of the new treatments and have significantly influenced WHO recommendations and guidelines. Dr. Guglielmetti emphasized the role of independent actors, including non-governmental organizations (NGOs), in evaluating and incorporating new treatments into global health policies. He also criticized the pharmaceutical industry for its limited role in informing the use of new drugs in treatment regimens, despite bringing them to market.
One of the key challenges highlighted by MSF is the high cost of delamanid, one of the drugs included in the newly recommended MDR-TB regimens. The Japanese pharmaceutical company Otsuka, through its exclusive licensee Viatris, has kept the price of delamanid excessively high, limiting access for many patients. MSF has called on Otsuka and Viatris to stop blocking the production of cheaper generic versions of delamanid and to immediately share the drug with other companies interested in making affordable versions. Christophe Perrin, MSF’s TB advocacy pharmacist, emphasized the urgent need for these companies to make delamanid more affordable for patients with drug-resistant TB.
The development of shorter, more tolerable, and all-oral treatment options for MDR-TB/RR-TB represents a major advancement in the fight against this difficult and deadly disease. However, access to these treatments must also be addressed by lowering prices and making them more widely available. The WHO’s recommendations mark a significant milestone, but the success of these new guidelines relies heavily on the affordability and accessibility of key drugs like delamanid. Lowering the price of delamanid could reduce the total cost of a 9-month MDR-TB regimen from $2,000 to less than $400, making it more accessible to patients in low- and middle-income countries.
India, which accounts for 27% of global TB cases, stands to benefit greatly from the new regimens. The Indian Council of Medical Research (ICMR) conducted a study that showed over 90% cure rates with a significant drop in mortality rates using the new regimen. As a result, India is set to roll out training for the novel oral drug regimen recommended by the WHO. This training will begin by the end of August or the first week of September in Mumbai and will expand to other locations. The training will cover monitoring for adverse effects and determining the appropriate line of treatment. It will be provided to state TB officers, medical officers, and master trainers, who will then train others at the district and community levels.
The new regimen, known as BPALM, is more effective, shorter in duration (six months), and has fewer side effects than the current treatment. It also helps prevent transmission, making it an important tool in managing TB. The decision to implement this regimen was based on promising findings from the ICMR study. The proper procurement of drugs like bedaquiline and pretomanid is essential for the success of this initiative. Rate contracts have been established for these drugs, and there is also a focus on scaling up molecular tests, like the nucleic acid amplification test (NAAT), to identify more cases of drug-resistant TB.
The WHO’s rapid communication about upcoming updates to the treatment of drug-resistant tuberculosis (DR-TB) includes a new 6-month treatment regimen using bedaquiline, delamanid, linezolid, and either levofloxacin or clofazimine. There will also be a group of 9-month regimens for treating patients with multi-drug resistant or rifampicin-resistant TB without fluoroquinolone resistance. This announcement is being made in advance of the updated WHO consolidated guidelines, which are expected to be released in early 2025. The goal of this communication is to inform national TB programs and other stakeholders about significant changes in DR-TB treatment.
The new treatment regimens are intended to be more effective and reduce the duration of treatment for DR-TB. The use of bedaquiline, delamanid, and linezolid in combination is a significant update from previous guidelines. Levofloxacin and clofazimine may also be used in combination with these medications. The announcement highlights the importance of rapid transition and planning at the country level to implement these changes. The WHO is working to accelerate the response to DR-TB and improve access to effective treatment. They are also striving to increase the use of rapid diagnostics and to address systemic barriers to TB care, such as stigma and discrimination.
The updated guidelines are based on the latest scientific evidence and input from experts and stakeholders. They will also consider the impact of COVID-19 on the treatment of TB and DR-TB patients. The use of bedaquiline and delamanid has been shown to be effective in treating DR-TB, but access to these medications has been limited in many countries. The 6-month regimen is a promising option for reducing the treatment duration and improving patient outcomes. The 9-month regimens will be particularly useful for patients who do not have resistance to fluoroquinolones. It is important for national TB programs to begin planning and preparing for the implementation of these changes in DR-TB treatment.
This announcement serves as a call for action to improve the treatment of DR-TB and ultimately end the global TB epidemic. The WHO will continue to monitor the implementation and impact of these updates and make adjustments as needed. With the new regimens and continued efforts, there is hope for better outcomes and control of DR-TB around the world. Governments and pharmaceutical companies must prioritize the availability and affordability of important drugs like delamanid in the fight against TB. By ensuring that these lifesaving treatments are accessible to all who need them, we can make significant strides in combating MDR-TB and improving global health outcomes.