Promising New Data on Pediatric Use of Pretomanid in Children with Drug-Resistant Tuberculosis Presented at 2025 Union Conference

Positive results mark an important step forward in efforts to develop effective treatments for children with drug-resistant TB

COPENHAGEN, Denmark, Nov. 19, 2025 /PRNewswire/ -- New interim data from the IMPAACT 2034 study presented today as a late-breaking oral abstract at the 2025 Union World Conference on Lung Health demonstrates that a single dose of pretomanid, in female children with rifampicin-resistant tuberculosis (RR-TB), was safe, well-tolerated, and achieved pharmacokinetic exposures comparable to adults. These findings are an important advance toward the goal of making pretomanid-containing regimens available to children.

Pretomanid is a nitroimidazole antibiotic approved for use as part of BPaL-based regimens (comprised of bedaquiline, pretomanid, and linezolid) in adults with drug-resistant tuberculosis (DR-TB). To address the urgent need for child-friendly formulations, 10 mg and 50 mg dispersible tablets were developed and initially studied to confirm they achieved the same drug exposure levels as the existing adult formulation before being evaluated in pediatric populations. IMPAACT 2034 is the first clinical study to evaluate pretomanid pharmacokinetics (PK), safety, and acceptability in children with TB.

The Phase 1 IMPAACT 2034 study enrolled 28 female children with RR-TB, including 7 children living with HIV, from South Africa (n=26) and Thailand (n=2). It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). IMPAACT 2034 is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, which receives support from NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health, all parts of NIH. Additional funding is provided by TB Alliance. Participants were divided into four weight-based cohorts and received a single dose of pretomanid (20-200 mg) using either the marketed adult tablet or pediatric dispersible formulations. Weights ranged from 6.9 to 56.8 kg and ages from 0.6 to 17.6 years.

"As the first clinical study of pretomanid in children, these findings provide foundational data that will guide future development toward expanding access to pretomanid for children with drug-resistant TB," said Dr. Eugene Sun, Senior Vice President of R&D at TB Alliance. "By demonstrating that pediatric formulations achieve the expected drug levels and are well tolerated, this research underscores the vital role of continued innovation in developing effective, child-friendly therapies for drug-resistant TB."

The primary objective was to confirm weight-based dosing strategies. Participants were followed for two weeks after dosing, and an interim PK and safety analysis was conducted.

Key findings include:

• Comparable drug exposure: Pretomanid exposures in children were comparable to those observed in healthy adults and adults with TB, across all weight-based cohorts.
• Favorable safety profile: A single dose of pretomanid was well tolerated, with no unexpected safety signals reported in any cohort.

The study successfully characterized the PK profile of pretomanid across age and weight groups, confirming modeled dosing predictions and supporting progression to the next phase of pediatric evaluation.

The enrollment of male children in this study was not recommended by the U.S. Food and Drug Administration due to concerns of testicular toxicity in male rodents (but not primates) during pre-clinical studies. Data from a human semen study in adults with DR-TB were reassuring, and there is a plan to enroll male children in a subsequent, multidose study.

"Developing MDR-TB specific therapies tailored to the needs of children is critical to closing the treatment gap for TB," said Dr. Sharon Nachman, Principal Investigator and Chair at the IMPAACT Network. "Ensuring that children with TB have access to effective, tolerable, and child-friendly treatment options will significantly improve outcomes and quality of life."

About Pretomanid
Pretomanid is a tuberculosis (TB) drug developed by TB Alliance that was first approved by the U.S. Food and Drug Administration in 2019 for the treatment of highly drug-resistant forms of TB for use in a combination regimen with bedaquiline and linezolid (known as the BPaL regimen). Pretomanid-based regimens are now included in WHO guidelines for drug-resistant TB and are being rapidly and widely adopted for use around the world. Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazole oxazines. Novel compounds are important in pursuing new TB treatments because resistance to drugs and drug classes currently used to treat TB is widespread.

About IMPAACT 
The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network is a global collaboration of investigators, institutions, community representatives, and other partners with a mission to improve health outcomes in infancy, childhood, adolescence, pregnancy, and postpartum among those who are impacted by or living with HIV, tuberculosis, and other related complications through the conduct of high-quality clinical trials. IMPAACT's vision and overall goal is to end the worldwide HIV epidemic among these populations. To achieve this goal, the IMPAACT Network evaluates novel and durable treatments for HIV, TB, and related diseases and conditions, strategies for antiretroviral treatment (ART)-free remission, and strategies to prevent and manage neuropsychological and mental health complications of HIV and its treatment. Overall support and funding for IMPAACT is provided by the National Institute of Allergy and Infectious Diseases (NIAID), with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the United States National Institutes of Health (NIH). For more information, please visit: www.impaactnetwork.org.

About the National Institutes of Health (NIH)
NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit: www.nih.gov.

About TB Alliance
TB Alliance is a not-for-profit organization dedicated to finding faster acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia's Department of Foreign Affairs and Trade, Cystic Fibrosis Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Gates Foundation, Germany's Federal Ministry of Research, Technology and Space (BMFTR) through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Korea International Cooperation Agency, MedAccess, Raoul Follerau Foundation, South Korea's Ministry of Foreign Affairs, United States Department of Defense Congressionally Directed Medical Research Programs (CDMRP), United States Department of State, United States National Institutes for Health – National Center for Advancing Translational Sciences (NCATS), United States National Institutes for Health – National Institute of Allergy and Infectious Diseases (NIAID), and Unitaid. For more information, please visit: www.tballiance.org.

SOURCE IMPAACT