pretomanid (PA-824) / Global Alliance for TB Drug Development - LARVOL DELTA

An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens. (PubMed, Curr HIV/AIDS Rep) - "While long-acting antiretroviral therapies (LA-ART) like cabotegravir/rilpivirine and lenacapavir exist, data on their safety and efficacy in pregnant individuals are limited...For active drug-resistant TB, the new 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) is not recommended in pregnancy due to limited safety data on pretomanid...While standard ART remains the recommended approach for HIV/TB co-infection in pregnancy, further research is crucial to establish the safety and efficacy of newer LA-ART and bedaquiline-based TB regimens in this high-risk population. Concerns around the safety of TPT in pregnancy remain unanswered and further prospective research is urgently needed."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Clinical best practices for caring for people with expanded resistance to newer TB drugs. (PubMed, IJTLD Open) - "While we await systematic studies of treatment approaches to generate the necessary evidence base, the clinical practices described here can be used to guide the programmatic care of people with strains of M. tuberculosis that have expanded resistance."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Application of antimicrobial drugs in Mycobacterium tuberculosis and research progress. (PubMed, Microb Pathog) - "In terms of treatment, new drugs such as bedaquiline, delamanid, and pretomanid have shown significant efficacy against MDR-TB and XDR-TB. Understanding the resistant genes and biochemical mechanisms of M. tuberculosis, developing drugs that disrupt its biofilms, optimizing drug combinations, and personalizing treatments are crucial for reducing tuberculosis mortality and controlling its spread, thus achieving WHO's goal of global tuberculosis eradication. Future research should focus on improving drug accessibility and affordability, and making significantly contributions to global public health goals."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Step Towards Tuberculosis Elimination – Advantages of Pretomanid Use in MDR-TB Patients (ERS 2025) - No abstract available

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Identification of Pretomanid drug resistance in clinical isolates of Multi-Drug Resistant (MDR) Mycobacterium tuberculosis from North India (ERS 2025) - No abstract available

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Targeting drug-resistant Mycobacterium tuberculosis: an integrated computational approach to identify DprE2 inhibitors. (PubMed, SAR QSAR Environ Res) - "Pretomanid and delamanid, two recently developed antitubercular drugs, are bicyclic nitroimidazoles that act as prodrugs, requiring activation by specific mycobacterial enzymes. Binding free energy calculations using the MM-GBSA method were then applied to refine the selection, identifying five potent lead molecules. These candidates show strong potential for further development as DprE2 inhibitors, offering a new path in the fight against drug-resistant tuberculosis."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

panTB-HM: A Pan-TB Regimen Targeting Host and Microbe (clinicaltrials.gov) - P2/3 | N=352 | Active, not recruiting | Sponsor: The Aurum Institute NPC | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Jan 2026 | Trial primary completion date: Sep 2025 ➔ Jan 2026

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

Therapeutic Management of an Immunocompromised Patient With Disseminated M. Avium Disease (ATS 2025) - "The patient was treated with clarithromycin, ethambutol, rifabutin, moxifloxacin, and cycloserine for two years, with amikacin added for the first six months, which led to hearing loss...A salvage regimen was initiated, including amikacin, tedizolid, clofazimine, ceftazidime/avibactam, isoniazid, delamanid, and ethambutol, as well as antiepileptic treatment and IFNγ administration...Dexamethasone plus intensified NTM treatment...Due to previous Gram-negative infections, his regimen was modified to include daptomycin, meropenem/vaborbactam, and colistimethate...He was placed on meropenem and ceftriaxone with clofazimine, isoniazid, linezolid, cycloserine, bedaquiline, and pretomanid. NeurologicaMl declinerequired intubation, and despite aggressive treatment, he ultimately succumbed to sepsis.ConclusionsThis case demonstrates the necessity for high clinical suspicion of mycobacterial infection in granulomatous diseases unresponsive to standard therapies. Effective..."

Clinical • CNS Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Otorhinolaryngology • Respiratory Diseases • Septic Shock • IFNG • IL12A

Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon. (PubMed, Acta Pharm Sin B) - "Promising drugs such as bedaquiline, delamanid, and pretomanid have been recently released, and 19 drug candidates are currently at different phases of clinical trials, addressing the problem of drug-resistant TB. Despite the persistent need for new treatments, TB research remains underfunded, highlighting the importance of collaborations between academia and the private sector in the advancement of anti-TB drug development. This review provides a perspective on the dynamic landscape of anti-TB drug discovery in recent years, offering hope for a more effective approach to combat this persistent global health threat."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

What Non-Profit Development of Pretomanid Can Teach About Paths to Innovation and Global Access to Treatments for Diseases of Poverty? (ISPOR 2025) - "OBJECTIVES: Pretomanid, developed by the non-profit TB Alliance, is one of only three drugs (pretomanid, bedaquiline, delamanid) approved in the past 40 years to treat pulmonary multidrug-resistant tuberculosis (MDR-TB). BPaL (bedaquiline, pretomanid, linezolid) or BPaLM (with moxifloxacin) regimens offer a 90% cure with 6 months treatment... Pretomanid’s development demonstrates the feasibility of drug development by an independent, non-profit firm. TB Alliance minimizes drug costs by eliminating cash distributions to shareholders (the distinguishing feature of non-profits) and eschewing returns from sales outside high-income countries. Without a cost-recovery mechanism, however, TB Alliance relies on philanthropy and grants to sustain operations and new development."

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Long term outcomes in drug resistant tuberculosis with Bedaquiline, Pretomanid and varying doses of Linezolid. (PubMed, J Infect) - "Structured dose reduction arms had comparable recurrence free cure rates as linezolid 600mg arm when given along with bedaquiline and pretomanid for 26 weeks in PreXDR TB. Most of the recurrences occurred within the first six months."

Clinical • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Treatment success rate and time to culture conversion under a prospective BPaL cohort study. (PubMed, IJTLD Open) - "The Indonesian BPaL OR showed a highly promising TSR of 97.6%, with 100% sputum conversion within 3 months. The lack of observed statistical differences in the TSCC across variables shows that the BPaL treatment will be equally effective in all patient groups."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance. (PubMed, J Biomol Struct Dyn) - "These investigations highlighted the DLM-tolerant G53D and Y65S and PTM-resilient Y133M (Ddn), L308P (FbiA), and C562W (FbiC) as candidate loss-of-function mutants of progressive research. The present results and interpretations could supply vital clues for protein engineering and drug development."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Effectiveness of the BPaL(M) Regimen for Drug-Resistant Tuberculosis in Ukraine under Programmatic Conditions. (PubMed, Clin Infect Dis) - "Bedaquiline, pretomanid, and linezolid, with or without moxifloxacin, have revolutionized treatment for drug-resistant tuberculosis. In Ukraine, we observed an 86% (n=394/460) success rate under programmatic conditions when drugs were accessible, exceeding prior estimates (58%) and aligning with trials (80-90%). However, access and implementation remain a concern in conflict-affected settings."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

The KasA inhibitor JSF-3285 improves the sterilizing activity of bedaquiline-pretomanid-containing regimens in a mouse model of tuberculosis. (PubMed, Antimicrob Agents Chemother) - "JSF-3285 is a promising preclinical candidate for tuberculosis that potently targets the Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA. In mouse models of acute, sub-acute, chronic, and relapse infection, JSF-3285 offers substantial activity in combination with bedaquiline and pretomanid, which could be applicable for both drug-sensitive and drug-resistant infections."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

RAD-TB: Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (clinicaltrials.gov) - P2 | N=315 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Suspended

Trial suspension • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

ACTG A5409 (RAD-TB): Study Protocol for a Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis. (PubMed, Res Sq) - P2 | "The experimental treatment arms will consist of a bedaquiline and pretomanid backbone (BPa) in combination with one of three oxazolidinones. Arm 2 will study linezolid (BPaL) at a dose of 600 mg daily, Arms 3A and 3B will study TBI-223 at 1200 mg and 2400 mg daily, respectively, and Arms 4A and 4B will study sutezolid at 800 mg and 1600 mg daily, respectively...Trials registration : ClinicalTrials.gov NCT06192160. Registered on January 5, 2024, https://clinicaltrials.gov/study/NCT06192160."

Journal • P2 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Diagnostic accuracy of nanopore sequencing for detecting Mycobacterium tuberculosis and drug-resistant strains: a systematic review and meta-analysis. (PubMed, Sci Rep) - "Studies on detecting resistance to bedaquiline, pretomanid, and linezolid are lacking. Sensitivity analyses reveal that retrospective study design, use of GridION, and use of Illumina whole-genome sequencing (WGS) decrease overall accuracy in detecting any drug-resistant MTB. Findings from both types of analyses, however, should be interpreted with caution because of the low number of studies and uneven distribution of studies in each subgroup."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Bedaquiline and linezolid regimens for multidrug-resistant tuberculosis: a systematic review and meta-analysis. (PubMed, J Bras Pneumol) - "MDR-TB treatment regimens including BDQ and LZD lead to significantly better patient outcomes. The combined bactericidal and protein synthesis-inhibiting effects of BDQ and LZD create a powerful therapeutic synergy. Adding pretomanid further enhances this effectiveness, highlighting its value in complex cases. Future research should focus on optimizing these regimens for safety and efficacy and explore adjunctive therapies to improve MDR-TB outcomes even further."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A PAN-USR TB Multi-Center Trial (clinicaltrials.gov) - P3 | N=610 | Not yet recruiting | Sponsor: Shenzhen Third People's Hospital

New P3 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Tuberculosis disease among people with HIV: therapeutic advances. (PubMed, Lancet HIV) - "Following recent research advances for drug-resistant tuberculosis, a 6-month regimen containing a potent combination of bedaquiline, pretomanid, linezolid, and moxifloxacin is a new standard for people with and without HIV. The tuberculosis drug development pipeline contains promising new therapeutics in various stages of development. To accelerate tuberculosis elimination, future research should focus on shortened treatment duration, and safer and effective therapeutics for tuberculosis-affected populations globally, including people with HIV, children, and pregnant people, and should assess newer modalities of treatment delivery."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Update in tuberculosis treatment: a scoping review of current practices. (PubMed, Breathe (Sheff)) - "Regimens based on bedaquiline or delamanid demonstrated high success rates and good tolerability. The BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) regimen was more effective and safer than the standard care, while shorter DR-TB regimens reduced costs and increased success rates...Though limited, paediatric studies suggest that shorter, safer regimens may benefit children. Evidence supports the adoption of shorter treatment regimens for both DR-TB and DS-TB to improve safety, effectiveness and cost-effectiveness, particularly in resource-limited settings."

Journal • Review • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Recent advancements in tuberculosis (TB) treatment regimens. (PubMed, J Family Med Prim Care) - "Drug-resistant TB poses significant hurdles, with multidrug-resistant (MDR) and rifampicin-resistant (RR) TB affecting 410,000 individuals, yet only 175,650 were diagnosed and treated. Advances in TB treatment include the World Health Organization's recommended 6-month BPaLM regimen (Bedaquiline, Pretomanid, Linezolid, Moxifloxacin), demonstrating 89% treatment success for MDR/RR-TB cases...Emerging drugs and regimens aim to shorten treatment duration and improve outcomes. This article reviews recent advancements in TB treatment regimens, diagnostics, and vaccines, emphasizing the importance of these innovations in addressing drug-resistant TB and improving global TB control efforts."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

3D spheroid model reveals enhanced efficacy of mannose-decorated nanoparticles for TB treatment. (PubMed, Nanomedicine (Lond)) - "We explored a combination therapy using bedaquiline and pretomanid encapsulated in polymeric nanoparticles (pNPs). Man-pNPs formulation showed superior intracellular bacterial inhibition in TB spheroid model compared to free drug combination and pNPs. This research underscores the potential of combination therapy, particulate-based inhaled drug delivery, and active targeting to advance efficient and patient-friendly TB treatments."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Urgent request for pretomanid label expansion to align with WHO guidelines and improve treatment accessibility and efficacy. (PubMed, IJTLD Open) - "The current EMA-approved label for pretomanid restricts its use to the regimen comprising bedaquiline, pretomanid and linezolid (BPaL) and only for extensively drug-resistant-TB or multidrug-resistant TB, "when antibiotics used for the latter form of TB do not work or cause unacceptable side effects." This restricted use implies that the older, prolonged and poorly tolerated regimens remain the recommended treatment for most cases of drug-resistant TB. The authors, representing many respiratory groups and societies, call for the label expansion of pretomanid to align with global guidelines, allowing for broader use."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis