Landmark clinical trial redefines multidrug-resistant tuberculosis treatment options
endTB Clinical Trial Offers Multiple New Shortened Drug Regimens to Treat Adults and Children with Multidrug–Resistant Tuberculosis
Paris, France – Clinical trial results presented for the first time today at the Union World Conference on Lung Health revealed evidence to support the use of four new, improved regimens to treat multi-drug resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB). The team—led by Médecins Sans Frontières (MSF), Partners In Health (PIH), and Interactive Research and Development (IRD) and funded by Unitaid—formed the endTB consortium and began this Phase III randomized controlled trial in 2017.
MDR/RR-TB is a disease caused by a TB bacterium that is resistant to rifampicin, one of the most powerful first-line antibiotics, plus/minus resistance to isoniazid. Roughly half a million people fall sick with MDR/RR-TB each year, and many die from it. Though a range of MDR-TB regimens are now in use around the world, many people are still treated with conventional treatments that are long (up to 24 months), ineffective (only 59% treatment success in 2018), and often cause terrible side effects, including acute psychosis and permanent deafness. Patients on these regimens must ingest up to 14,000 pills over the full course of treatment, and some have to endure months of painful, daily injections.
The trial found three new drug regimens that can deliver similar efficacy and safety to conventional treatments while reducing treatment time by up to two-thirds. The endTB regimens represent important alternatives for short MDR-TB treatment and complement the use of another highly effective, shorter MDR-TB regimen, called BPaLM, which is not suitable for certain populations. If recommended by the World Health Organization, these new patient-centered treatment regimens would empower clinicians to offer shortened MDR-TB treatment regardless of age, pregnancy, and comorbidities that are common among people with MDR-TB.
In addition, the trial supports the use of a fourth regimen as an alternative for people who cannot tolerate bedaquiline or linezolid; at least one of these two drugs is in every current World Health Organization-recommended regimen for MDR-TB.
The endTB trial enrolled a diverse group of 754 patients from seven countries (Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa). This included historically excluded populations like adolescents and those with comorbidities like substance-use disorders, and retained participants who became pregnant during the trial. The trial evaluated five nine-month treatment regimens, and randomization was outcome-adapted, meaning more patients were assigned to regimens that were producing better outcomes.
“We stand on the cusp of a significant breakthrough in the battle against MDR, a disease that disproportionately affects impoverished populations around the globe. Our results offer hope to those in dire need and underscore the urgency of continued research and innovation—and accountability of private companies that receive public funds—to address diseases that too often strike the most vulnerable among us. But the cost of some drugs remains a barrier. One example is delamanid which is still priced at 12-40 times higher than it should be according to an independently estimated cost to produce the drug,” said Carole Mitnick, ScD, Partners In Health Director of Research for the endTB project, Co-Principal Investigator of the study, and Professor of Global Health and Social Medicine at Harvard Medical School.
“For far too long, MDR-TB has loomed as a formidable threat with limited, poorly tolerated treatment options, but today, we unveil evidence for multiple innovative all-oral, shortened regimens that will allow patient-centered, individualized treatment of MDR-TB. This marks a pivotal moment in the fight against a disease that has plagued vulnerable populations worldwide. What makes these results even more remarkable is the diversity, and resulting generalizability, of this Phase III randomized controlled trial,” said Lorenzo Guglielmetti, MD, Médecins Sans Frontières Director for the endTB project and Co-Principal Investigator of the study.
“These results provide new hope for all those awaiting treatment for the most dangerous and difficult to treat forms of tuberculosis worldwide,” said Dr Philippe Duneton, Executive Director of Unitaid. “We have the gold-standard research. The drugs are already available where they are needed. If recommended, this high-quality evidence could quickly translate into better treatment options suitable for all people with drug-resistant tuberculosis.”
The endTB clinical trial evaluated five experimental regimens for MDR/RR-TB against the standard of care in two distinct analysis populations. endTB regimens 1, 2, 3, demonstrated non-inferiority to the control in both primary analysis populations, establishing their success in treating RR-TB. Regimens 1, 2, and 3 achieved favorable outcomes in 89.0%, 90.4%, and 85.2% of participants, respectively. Regimen 5 also showed a strong treatment response at 85.6% and was non-inferior to the control’s 80.7% in one of the primary analysis populations. While consistent results in both populations are needed to formally establish non-inferiority, regimen 5 holds promise as an alternative for patients unable to receive other recommended treatments.
True access to these new treatment options depends on removing all barriers to timely and high-quality care. These trial results could address a major barrier to care for many people and the endTB consortium will continue to advocate to improve access and affordability to quality TB care.
To read more about the clinical trial results, please visit endTB.org.
Press contacts:
Eric Hansen, Director of external relations, PIH ehansen@pih.org
Asad Taj, Press Manager, IRD media@ird.global
Hervé Verhoosel, Head of communications, Unitaid verhooselh@unitaid.who.int
Laura Garel, Communications Advisor, MSF laura.garel@tokyo.msf.org
About UNITAID
Unitaid saves lives by making new health products available and affordable for people in low- and middle-income countries. Unitaid works with partners to identify innovative treatments, tests and tools, helps tackle the market barriers that are holding them back, and gets them to the people who need them most – fast. Since it was created in 2006, Unitaid has unlocked access to more than 100 groundbreaking health products to help address the world’s greatest health challenges, including HIV, TB, and malaria; women’s and children’s health; and pandemic prevention, preparedness and response. Every year, these products benefit more than 300 million people. Unitaid is a hosted partnership of the World Health Organization.
About MSF
Médecins Sans Frontières / Doctors Without Borders (MSF) is an international, independent, medical humanitarian organization that delivers emergency aid to people affected by armed conflict, epidemics, natural disasters and exclusion from healthcare. Today, MSF has operations in nearly 70 countries.
MSF has been involved in tuberculosis care for over 30 years and opened its first programmes to treat multidrug-resistant TB in 1999. MSF has TB treatment projects in 30 countries; it is one of the largest non-governmental providers of treatment for drug-resistant TB. In 2022, 17,800 people started first-line treatment for tuberculosis in MSF programmes worldwide; 2,590 patients started drug-resistant tuberculosis treatment. For more information, visit: www.msf.org.
About PIH
Partners In Health is a global health organization relentlessly committed to improving the health of the poor and marginalized. PIH builds local capacity and work closely with impoverished communities to deliver high-quality health care, address the root causes of illness, train providers, advance research, and advocate for global policy change. PIH began treating MDR-TB in 1995 and has since implemented community-based treatment programs for MDR-TB in multiple countries, including Peru, Russia, Haiti, Lesotho and Kazakhstan. For more information, visit: www.pih.org.
About IRD
IRD is a global health delivery and research organization based in Dubai that works in 15 countries, including high-burden MDR-TB countries such as Pakistan, Indonesia, and Bangladesh. The IRD team leverages process and technology innovations to address global health delivery gaps, including the use of health market innovations such as social business models to engage private providers in lung health and diabetes care, as well as the use of performance-based incentives for community screeners and treatment supporters, patient incentives to enable treatment compliance, and the use of open source information technology platforms to allow close monitoring of patient care and program quality. For more information, visit www.ird.global.
Unitaid at the Union World Conference
Unitaid-backed programs and research studies will feature prominently at the Union World Conference on Lung Health. Highlights include the results of two major clinical trials evaluating multidrug-resistant tuberculosis (MDR-TB) treatment and prevention. This includes the results of the endTB clinical trial, which sought to find additional, all-oral, shorter treatment regimens for MDR-TB, and the TB-CHAMP trial, which led the first gold-standard evaluation into MDR-TB prevention for children.
Additional updates from Unitaid programs will share advances in TB diagnostics, preventive therapies, child medicines and more over the course of the conference. Join us for the following sessions.
Wednesday, 15 November
endTB clinical trial results: Innovation to guide practice in MDR/RR-TB treatment: efficacy and safety results of the endTB trial 10:15–11:45
From neglect to child-friendly options: Assisting countries implement improved TB treatment for children and adolescents 10:15–11:45
- Challenges faced by children taking anti-TB medication | 10:20–10:34
- Additional research in improving TB drug administration in children | 11:16–11:30
TB Preventive Therapy – how far are we? 16:45–18:15
Digital adherence technologies in TB care: key results and lessons from the Adherence Support Coalition to End TB (ASCENT) trial 18:30–20:00
Thursday, 16 November
Meet the French Team: opportunities to fund TB research and implementation programmes 8:00-9:00
Pharmacokinetics studies for better treatment of TB 8:30–10:00
- Pharmacokinetic-toxicity analysis of long-term linezolid use in children with MDR-TB | 8:41–8:48
- Palatability preferences in children; the swish-and-spit taste panel approach for formulation development | 9:30–9:37
The Union/CDC late-breaker session on TB (treatment and clinical trials) 10:15–11:45
- Efficacy and safety of levofloxacin preventive therapy in child and adolescent household contacts of multidrug-resistant TB: the TB-CHAMP double-blind placebo-controlled, cluster randomized trial | 10:38–10:47
Guarantee equitable and universal access to innovations in the fight against TB: Roundtable discuss at the Expertise France booth in the exhibition hall 14:00–15:00
BENEFIT Kids Satellite Session: Better Evidence and Formulations to Improved Multidrug-Resistant Tuberculosis Treatment in Children 18:30–20:00
Community-led “test and treat” advocacy and community engagement for pandemics: lessons from India and Zimbabwe 16:00–16:45
Friday, 17 November
Next-generation sequencing for TB detection 7:15–8:15
The impact of digital adherence technologies on TB care: Results from ASCENT and other studies 15:00–16:30
Researchers sharing with communities: Results from the endTB trial 18:00–18:45
Upgrading the TB diagnostics toolbox – what’s needed to ensure diagnosis for all? 17:00–17:45
Panelist Discussion on: Recent advances in TB-drug resistance detection using Next Generation Sequencing 18:30-20:00
Saturday, 18 November
Drug sensitive TB: Treatment and Care 8:30–10:00
- The socio-economic impact of the COVID-19 pandemic in households having children with rifampicin-resistant TB: Qualitative study from South Africa, India and Philippines | 9:29-9:38
TB stigma, discrimination and equity 13:15–14:45
- Stigma in households of children with rifampicin-resistant TB in South Africa, India and the Philippines | 13:20–13:29
Global policy and evidence for the use of targeted next-generation sequencing for the detection of TB drug resistance 13:12–14:45
- Presentation of the primary evidence on the diagnostic accuracy, cost-effectiveness, and acceptability of targeted next-generation sequencing, generated through Unitaid’s Seq&Treat project
In a special session held in advance of the Union Conference, Unitaid and the World Health Organization will convene national TB program representatives from more than 25 high-burden countries and technical partners to discuss progress in implementation, share available results to date, and identify key implementation bottlenecks to unlock the TB response and reach the most vulnerable with affordable, accessible solutions without delay.
The Union World Conference on Lung Health is the largest gathering of researchers, policymakers, global health advocates and others involved in advancing TB response and improving respiratory health for all. Follow all our news from the week here.
Partnership report: Unitaid and the Global Fund to Fight AIDS, Tuberculosis and Malaria
In our newly released Partnership Report, we highlight how the Global Fund and Unitaid collaborate to accelerate equitable access to lifesaving health products that prevent, detect and treat HIV, TB and malaria. By combining Unitaid’s investments in innovative new health products with the Global Fund’s proven ability to take those tools to scale around the world, we increase return on investment, save more lives and reach the health-related Sustainable Development Goals more quickly.
The Global Fund and Unitaid each play a distinct and complementary role in advancing access to new products and approaches to save lives. Unitaid connects a broad range of partners to identify and create innovative new health products, and then brings them to market quickly and affordably for the people that need them most. The Global Fund, as one of the largest providers of key health commodities, supports over 120 countries in deploying these innovations at scale and at affordable prices.
New products and novel approaches to fight HIV, TB and malaria can transform care, averting countless cases of illness and death. But lifesaving medicines and tools will have limited impact without a concerted effort to ensure access for all who need them. Our collaboration spans all three diseases and has included ensuring equitable access to next-generation mosquito nets to stop malaria-carrying mosquitoes, game-changing treatments for HIV, and more effective TB preventive therapy.
A joint analysis by Unitaid and the Global Fund estimated the return on investment and the impact these health innovations will have on the death toll from the three diseases between 2024-2026. That review showed that health innovations maximize the impact of investments into the Global Fund and broader HIV, TB, and malaria efforts, accelerating the overall response and delivering the same reduction in deaths more than three years faster. The health and economic gains from every dollar invested in the three diseases are 16% higher with health innovations like those piloted by Unitaid and scaled up by the Global Fund.
Read the full report here.
Partnership report: Unitaid and the Global Fund to Fight AIDS, Tuberculosis and Malaria
Unitaid welcomes J&J’s announcement not to enforce patents for vital TB drug
Unitaid applauds Johnson & Johnson’s decision, announced Friday 29 September, not to enforce its secondary patents for bedaquiline, a critical medicine for treating drug-resistant tuberculosis (DR-TB). The decision will affect people in 134 low- and middle-income countries, many of which have the highest burden of disease and have struggled to supply the critical medicine due to high costs.
This news comes after months of campaigning by the TB community, including an open letter from Unitaid’s Executive Director to J&J dated 22 September urging immediate action.
“Bedaquiline underpins all the shorter regimens for treating DR-TB, effectively holding the key to tackling drug resistance and turning the tide on this dangerous and debilitating form of the disease,” said Dr Philippe Duneton, Executive Director of Unitaid.
“Unitaid welcomes the significant step to improve access to this vital TB medicine and is pleased to see that the scope of countries covered includes upper-middle income countries that are often left out of access agreements.”
“Unaffordable medicines, diagnostic challenges and insufficient access to services have created a situation in which most people suffering from DR-TB never get treated. J&J’s decision will help progress efforts to address the high cost of treatment. Unitaid has invested close to US$300 million over the past decade to improve DR-TB testing and treatment and will continue to support efforts to improve DR-TB care. We are pleased to see J&J playing its part to enable critical medicines to reach communities that need them,” said Dr Duneton.
To increase legal certainty for generic manufacturers, Unitaid urges J&J to withdraw their secondary patents in low- and middle-income countries, including any pending applications pertaining to bedaquiline. In the interim, the announcement from J&J is a significant move in the right direction.
Media contact:
For more information and media requests:
Hervé Verhoosel
Head of Communications and Spokesperson
M: +33 6 22 59 73 54
verhooselh@unitaid.who.int
Johnson & Johnson pricing agreement for critical TB drug still unfairly restricts access in countries where the need is greatest
- Open letter from Unitaid’s Executive Director calls on the drug company to drop secondary patents for the drug-resistant TB (DR-TB) medicine bedaquiline, and to make negotiated rates available to all countries, regardless of how they purchase drugs.
- The letter follows advocates’ unanswered calls for broad access to bedaquiline, which is critical to achieving the reduction in TB agreed at the United Nations High-Level Meeting on 22 September.
- Bedaquiline is a vital component of all shorter treatment regimens for DR-TB, the most deadly and difficult to treat form of TB that affects millions of people worldwide.
- A recent agreement between Johnson & Johnson and the Global Drug Facility lowers the price of a six-month supply of bedaquiline to US$130, but the deal is an incomplete solution that will restrict access to lower cost medicines in the near future.
- Upcoming competition from multiple generic manufacturers is expected to lead to lower prices, but these products will remain unavailable in the countries with the greatest MDR-TB burden.
Geneva – In an open letter to the Chief Executive Officer of Johnson & Johnson (J&J), Unitaid, while acknowledging the investments J&J has made to develop and market innovative medicines to treat tuberculosis (TB), expressed its concern that the recent agreement between J&J and the Global Drug Facility (GDF) to lower the price of bedaquiline is an incomplete solution that will hinder access long-term.
Drug-resistant TB (DR-TB), the most dangerous and deadly form of TB, affects nearly half a million people every year. Because so few currently access appropriate treatment, millions of people worldwide are in critical need of bedaquiline.
The J&J/GDF agreement saw a historic 55% price reduction of the drug, which is a welcome step in increasing access to this critical medicine that underpins all shorter regimens for treating DR-TB. However, the agreed price of US$130 for a six-month supply of J&J’s SIRTURO® (bedaquiline) is only available to countries when purchasing through GDF, which effectively excludes several countries where the rates of MDR-TB are highest.
Additionally, following the Indian Patent Office’s rejection of J&J’s secondary patent application for bedaquiline in the country in April, several generic manufacturers are expected to enter the Indian market, home to the highest number of people with MDR-TB in the world. This is likely to further reduce the cost of generic bedaquiline but secondary patents in place in low- and middle-income countries will restrict availability to these vital medicines in a subset of countries with the highest burden of disease.
Unitaid is calling on J&J to remove secondary patents or provide a comprehensive license to generics and allow all countries to purchase bedaquiline at the negotiated rates, including those excluded from the agreement or not procuring through GDF.
This follows numerous advocates’ unanswered calls for equitable access to bedaquiline in recent months, including action from nations not able to benefit from access prices such as South Africa, Belarus, and Ukraine, among others.
Meeting these demands is essential to fulfilling the commitment made by heads of state at the United Nations High-Level Meeting on TB on 22 September to reach 1.5 million people with DR-TB treatment by 2027.
Unitaid’s open letter to J&J is reproduced in full here.
Media contact:
For more information and media requests:
Hervé Verhoosel
Head of Communications and Spokesperson
M: +33 6 22 59 73 54
verhooselh@unitaid.who.int
Bill & Melinda Gates Foundation doubles its contribution to Unitaid to US$100 million over 5 years
The Bill & Melinda Gates Foundation announced a long-term commitment of $100 million to Unitaid to bring faster access to health products in low- and middle-income countries. This funding doubles the foundation’s previous commitment and will support Unitaid’s work to accelerate the introduction and delivery of new lifesaving solutions at equitable scale, including those for maternal and newborn health.
The foundation highlighted that Unitaid’s unique approach helps reach the health-related targets of the Sustainable Development Goals more quickly.
“It takes far too long for lifesaving products to get from approval to widespread adoption. For over 15 years, Unitaid has played a pivotal role in speeding up that process – developing new health innovations, then working with organizations like the Global Fund to get them to people faster,” said Bill Gates, co-Chair of the Bill & Melinda Gates Foundation. “We’re on the cusp of exciting new innovations that will help accelerate progress on HIV, TB, and malaria, as well as maternal and child health. By doubling our foundation’s commitment to Unitaid, we hope to get these tools in the hands of health workers in time to save millions of lives.”
The Bill & Melinda Gates Foundation has been a supporter of Unitaid since its inception and serves as a member of Unitaid’s Executive Board. Since our creation, they have contributed a total of US$150 million to Unitaid’s work to fast-track the development of lifesaving tests, treatments and tools and speed up access for the people who need them most. With support from donors like the Gates Foundation, Unitaid has unlocked access to more than 100 groundbreaking products that are now considered the gold standard for fighting HIV, tuberculosis and malaria, improving women’s and children’s health, and strengthening pandemic preparedness and response.
Unitaid thanks the Gates Foundation for its ongoing support and the new funding, which will help us find new solutions to the most pressing global health challenges.
Read the full press release here.
Media contact:
For more information and media requests:
Hervé Verhoosel
Head of Communications and Spokesperson
M: +33 6 22 59 73 54
verhooselh@unitaid.who.int