CYP2C19 inhibitors(cytochrome P450 family 2 subfamily C member 19 inhibitors), CYP2C8 inhibitors(cytochrome P450 family 2 subfamily C member 8 inhibitors), Cell wall inhibitors

+ [2]

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Multidrug resistant pulmonary tuberculosisTuberculosis, Multidrug-ResistantExtensively Drug-Resistant Tuberculosis+ [4]

Inactive Indication

Infectious Lung Disorder

Originator Organization

Novartis Pharma AG

Active Organization

Viatris, Inc.Mylan IRE Healthcare Ltd.

Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd.

+ [4]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (14 Aug 2019),

Extensively Drug-Resistant TuberculosisTuberculosis

RegulationSpecial Review Project (CN), Fast Track (US), Orphan Drug (KR)

Structure

Molecular FormulaC14H12F3N3O5

InChIKeyZLHZLMOSPGACSZ-NSHDSACASA-N

CAS Registry187235-37-6

Clinical Trials associated with Pretomanid

NCT06192160 / Not yet recruitingPhase 2IIT

A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).
A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)].
The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.

Start Date10 Jan 2025

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

NCT06441006 / Not yet recruitingPhase 3IIT

Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis (PRISM-TB)

PRISM-TB is an international, multicenter, open-label, randomized, controlled, pragmatic, stratified medicine, treatment shortening, noninferiority Phase 3 clinical trial for fluoroquinolone-susceptible multidrug-resistant/rifampin-resistant pulmonary tuberculosis (FQ-S MDR/RR-TB).
The trial objective is to evaluate whether stratified medicine treatment strategies for FQ-S MDR/RR-TB, defined by a pre-specified risk stratification algorithm, have noninferior efficacy to a one-size-fits-all control regimen (the local standard-of-care [SOC] regimen consistent with preferred regimen(s) in international guidelines), as measured by TB-related unfavorable outcomes at Week 73.

Start Date01 Nov 2024

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT03896750 / RecruitingPhase 1IIT

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Pretomanid in Participants With Renal Impairment Compared to Participants With Normal Renal Function

This is a Phase 1, open-label, single-dose, sequential group study to compare the safety and pharmacokinetics (PK) of pretomanid in the following groups of participants: 1) participants with severe renal impairment including those with end stage renal disease (ESRD) not on dialysis, and participants with mild or moderate renal impairment, designated as Groups 2, 3, and 4, respectively; and 2) participants with normal renal function matched to the above renal impairment groups, designated as Groups 1A, 1B, and 1C, respectively.
The study will be conducted following a reduced PK study design in Part A. Part A will enroll participants from Group 1A (i.e., 6 healthy matched controls) and Group 2 (i.e., 6 participants with severe renal impairment and ESRD, not on dialysis). A decision to proceed to Part B will be made after the PK of pretomanid, and safety in participants enrolled in Part A have been reviewed. If Part A demonstrates at least a 50% increase in pretomanid area under the plasma concentration-time curve (AUC) in Group 2 (severe renal impairments and ESRD, not on dialysis) relative to the exposures in Group 1A (matched participants with normal renal function), then the reduced PK study will extend to the full PK study to enroll participants into Part B (i.e., to investigate mild and moderate renal impairment). All Part B groups (1B, 1C, 3, and 4) will be enrolled concurrently.
If the reduced PK study shows at least a 50% increase in AUC in patients with severe renal impairment and patients with ESRD not yet on dialysis relative to the matched healthy controls, a "full PK" renal impairment study in patients with all intermediate levels of renal function impairment should be conducted. Otherwise, no further study is recommended.
The approximate patient involvement will be 3 months. The primary objective is to evaluate the PK profiles of pretomanid in plasma and urine after a single oral dose of 200 mg in participants with renal impairment compared to matched healthy controls.

Start Date27 Mar 2024

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with Pretomanid

100 Translational Medicine associated with Pretomanid

100 Patents (Medical) associated with Pretomanid

398

Literatures (Medical) associated with Pretomanid

01 Dec 2024·Journal of Clinical Tuberculosis and Other Mycobacterial Diseases

Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis

Review

Author: Rivera, Christina G ; Zeuli, John D ; Johnson, Tanner M ; Lee, Grace

Mycobacterium tuberculosis (TB) remains the leading cause of infection-related mortality worldwide. Drug resistance, need for multiple antimycobacterial agents, prolonged treatment courses, and medication-related side effects are complicating factors to TB cure. The introduction of treatment regimens containing the novel agents bedaquiline, pretomanid, and linezolid, with or without moxifloxacin (BPaL-M or BPaL, respectively) have substantially reduced TB-related morbidity and mortality and are associated with favorable rates of treatment completion and cure. This review summarizes key information on the pharmacology and treatment principles for moxifloxacin, bedaquiline, delamanid, pretomanid, linezolid, and tedizolid in the treatment of multi-drug resistant TB, with recommendations provided to address and attenuate common adverse effects during treatment.

01 Nov 2024·IJTLD OPEN

Experience of piloting BPaLM/BPaL for DR-TB care at selected sites in Pakistan

Article

Author: Foraida, S. ; Zafar, F. ; Ismail, A. ; Fatima, R. ; Khan, M.A. ; Khan, N. ; Muzaffar, N. ; Ghafoor, A. ; Gupta, A. ; Shahid, S. ; Khan, A.W. ; Juneja, S.

<sec><title>BACKGROUND</title>Pakistan ranks fourth globally in terms of high drug-resistant TB (DR-TB) burden, with approximately one-third of cases resistant to fluoroquinolones. Bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM/BPaL) offers an opportunity for most DR-TB patients to benefit from a shorter, all-oral, well-tolerated and more effective treatment.</sec><sec><title>METHODS</title>We conducted a retrospective cohort study to pilot the BPaLM/BPaL regimen at four selected sites in two provinces of Pakistan, i.e. Punjab and Khyber Pakhtunkhwa. Data were extracted and analysed using electronic medical records from the program. Descriptive statistics, survival analysis and binary logistic regression analysis were employed.</sec><sec><title>RESULTS</title>A total of 116 patients took treatment between October 2022 and February 2023. The treatment success rate was 96%, with 3% deaths and <1% loss to follow-up. Patients typically completed treatment in 26.2–26.7 weeks for BPaLM and BPaL, respectively. No serious adverse events were observed. The most common side effects included QTcF prolongation (BPaLM: 55%, BPaL: 84%), haematological events (BPaLM: 32%, BPaL: 34%), and gastrointestinal problems (BPaLM: 36%, BPaL: 25%).</sec><sec><title>CONCLUSION</title>The BPaLM/BPaL regimens for DR-TB are highly effective with minimal adverse events and feasible to implement in routine program circumstances.</sec>

01 Nov 2024·Drug Resistance Updates

Widespread loss-of-function mutations implicating preexisting resistance to new or repurposed anti-tuberculosis drugs

Article

Author: Gorman, Bria M ; Modlin, Samuel J ; Elghraoui, Afif ; Conkle-Gutierrez, Derek ; Modlin, Samuel J. ; Gorman, Bria M. ; Valafar, Faramarz ; Thosar, Nachiket

BACKGROUNDFive New or Repurposed Drugs (NRDs) were approved in the last decade for treatment of multi-drug resistant tuberculosis: bedaquiline, clofazimine, linezolid, delamanid, and pretomanid. Unfortunately, resistance to these drugs emerged faster than anticipated, potentially due to preexisting resistance in naïve strains. Previous investigations into the rapid emergence have mostly included short variants. For the first time, we utilize de novo-assembled genomes, and systematically include Structural Variations (SV) and heterogeneity to comprehensively study this rapid emergence. We show high prevalence of preexisting resistance, identify novel markers of resistance, and lay the foundation for preventing preexisting resistance in future drug development.METHODSFirst, a systematic literature review revealed 313 NRD resistance variants in 13 genes. Next, 409 globally diverse clinical isolates collected prior to the drugs' programmatic use (308 were multidrug resistant, 106 had de novo assembled genomes) were utilized to study the 13 genes comprehensively for conventional, structural, and heterogeneous variants.FINDINGSWe identified 5 previously reported and 67 novel putative NRD resistance variants. These variants were 2 promoter mutations (in 8/409 isolates), 13 frameshifts (21/409), 6 SVs (9/409), 35 heterogeneous frameshifts (32/409) and 11 heterogeneous SVs (12/106). Delamanid and pretomanid resistance mutations were most prevalent (48/409), while linezolid resistance mutations were least prevalent (8/409).INTERPRETATIONPreexisting mutations implicated in resistance to at least one NRD was highly prevalent (85/409, 21 %). This was mostly caused by loss-of-function mutations in genes responsible for prodrug activation and efflux pump regulation. These preexisting mutations may have emerged through a bet-hedging strategy, or through cross-resistance with non-tuberculosis drugs such as metronidazole. Future drugs that could be resisted through loss-of-function in non-essential genes may suffer from preexisting resistance. The methods used here for comprehensive preexisting resistance assessment (especially SVs and heterogeneity) may mitigate this risk during early-stage drug development.

News (Medical) associated with Pretomanid

25 Mar 2024

·www.prnewswire.com

New PeerLINC Knowledge Hub will Leverage Local Expertise and Experience to Accelerate New, More Effective TB Cures Around the World

Hub will focus on supporting global use of new treatments that effectively treated drug-resistant TB in 98% of Filipino participants MANILA, Australia, March 24, 2024 /PRNewswire/ -- TB Alliance's new Peer-to-Peer Learning for Innovative Cures (PeerLINC) Knowledge Hub launched today in Manila, with funding from the Australian Government through the Partnerships for a Healthy Region initiative. PeerLINC, operating in partnership between TB Alliance and the Tropical Disease Foundation, Inc. (TDF), and in close collaboration with the Department of Health, Philippines, will help countries implement best practices in the treatment of drug-resistant tuberculosis (DR-TB) to help speed the worldwide programmatic implementation of innovative, more effective treatments for the disease, starting with the World Health Organization (WHO)-recommended six-month, all-oral BPaL/M regimens, composed of the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without moxifloxacin (M). PeerLINC will provide practical training and technical assistance to countries to support this objective, via experts from the Philippines and the Department of Health, including Lung Center of the Philippines and the National TB Reference Laboratory (NTRL). The Philippines has successfully and rapidly deployed new treatments through participation in TB Alliance's Leveraging Innovation for Faster TB Treatment (LIFT-TB) initiative. "TB Alliance works to minimize the gap between research and access, ensuring people anywhere in the world can have access to new treatments as soon as possible, maximizing the number of lives and livelihoods saved," said Sandeep Juneja, Senior Vice President of Market Access at TB Alliance. "PeerLINC will make training and knowledge on new treatments available swiftly and efficiently to ensure their rapid adoption and roll out. We are proud to launch PeerLINC in the Philippines with DOH and TDF and establish the first Knowledge Hub on the introduction of new DR-TB regimens, and we are grateful for the support of Australia in helping make this a reality." "It is important for the Philippines to share our knowledge and experience in using the BPaL/M regimens," said Dr. Mamel Quelapio, TDF Board of Trustees member and Programmatic Implementation Lead at PeerLINC. "DOH's leadership through the Disease Prevention and Control Bureau in partnership with TDF and TB Alliance in the LIFT-TB initiative has led to improved outcomes and treatment experiences for people. We are eager to help new treatments reach far and wide." The BPaL/M regimens combine the antibiotics bedaquiline (B), pretomanid (Pa), linezolid (L) with or without moxifloxacin (M). The BPaL regimen was first clinically studied by TB Alliance and the BPaL/M regimens are now recommended by WHO as the standard of care treatment for the vast majority of people with DR-TB. Prior to the initial study of the BPaL regimen, global treatment success rates for DR-TB were less than 50% and treatment options were limited, expensive, toxic, and lengthy – requiring individuals to take more than 14,000 pills over the course of treatment, which could last from nine months to two years or longer. Data to date reveals treatment success rates of 90% or higher with BPaL/M, in addition to reduced treatment duration and approximately 95% lower pill burden. TB Alliance's LIFT-TB initiative, which is co-funded by GDEF/KOICA, the South Korean Development agency, helped accelerate implementation of the regimen in the Philippines, Indonesia, Kyrgyzstan, Myanmar, Ukraine, Uzbekistan, and Vietnam. Interim data from these countries shows an average success rate of 92.5%, with the Philippines program reporting a 98% cure rate. Several key high-burden countries around the world, including the early adopting LIFT-TB countries, are now rolling out BPaL/M in their national programs. However, some countries have moved more slowly. Leveraging a group of experts and the experience garnered from those who have rapidly and successfully implemented the BPaL/M regimens, PeerLINC will focus on assisting other countries in doing the same. "In the Philippines, the new regimen exceeded all expectations," said Dr. Irene Flores, Medical Officer of the Jose B. Lingad Memorial Medical Center and Head of PeerLINC. "Every country with drug-resistant TB can benefit from widespread implementation of the best available TB treatment. With BPaL/M, we see a path toward transforming DR-TB treatment for everybody, anywhere in the world." "I tried everything before I was given BPaL as part of the research program," said Joegene Mangilaya, a participant from the Philippines who was treated with the BPaL regimen. "I was losing hope that I'd be cured, but shortly after I started on this new regimen, my body felt stronger and I had a new hope for my health and future. It is important to speed the availability of life-saving new therapies everywhere they are needed – the work of PeerLINC will help save lives." PeerLINC will offer support such as advice, assistance, training materials, tools, guides, and other materials to TB programs, clinicians, lab specialists, and community organizations, all delivered through peer-to-peer learning models. Trainings will be provided in-person in the Philippines or in the beneficiary country or remotely through virtual meetings. The expert team from PeerLINC will continue to guide countries after trainings, as they work to implement the regimens. A delegation from Peru is scheduled to visit PeerLINC in April 2024 and will be the first to receive training on BPaL/M from PeerLINC and its partners in the DOH. "We are excited to visit the PeerLINC Knowledge Hub and work with experts from the early implementers of the short, highly effective treatments for drug-resistant tuberculosis," said Dr. Valentina Alarcón, Executive Director at the Directorate of Tuberculosis Prevention and Control - MINSA Peru. "The communities affected by resistant tuberculosis in Peru deserve the best possible experiences and treatment schemes and we are taking measures to access the BPaL and BPaL/M regimens and make them available to people throughout Peru in a timely and rapid manner. Our experience with PeerLINC will help us achieve those goals." About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first designed and clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Prior to the initial BPaL clinical trial, less than one-third of drug-resistant TB patients around the world were being successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. 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, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jessica Wiggs, +1 (646) 616-8613 / [email protected] SOURCE TB Alliance

Drug ApprovalClinical Study

24 Mar 2024

·www.prnewswire.com

Australian Government Grants TB Alliance an Award to Help Bolster Clinical Research and Improve Access to New Treatments for Drug-Resistant TB

AUD 17 Million Grant over 5 Years Will Fund Next-Generation TB Cures CANBERRA, Australia, March 24, 2024 /PRNewswire/ -- The Australian Government, through the Partnerships for a Healthy Region initiative, has announced a new AUD 17 million grant to support work with TB Alliance through its Product Development and Access Partnerships program. The funding will contribute toward the completion of the NC-009 Pan-Phase 2 clinical trial and also help establish and sustain the Peer-to-Peer Learning for Innovative Cures (PeerLINC) Knowledge Hub in Manila, which will disseminate best practices to help speed the programmatic implementation of innovative, effective tuberculosis treatments, including the World Health Organization (WHO) recommended six-month, all-oral BPaL/M regimens for drug-resistant tuberculosis (DR-TB). "Drug-resistant TB is an increasing threat to the health and well-being both in Australia and in our neighbouring countries, and in many low- and middle-income countries around the world," said the Hon. Pat Conroy, Minister for International Development and the Pacific. "We are proud of our continued support of the work of TB Alliance, and to help in the rollout of the BPaL/M regimens and to support the development of the next generation of new TB treatments. These are important steps in the effort to end TB as a major health threat by 2030." PeerLINC, which will operate in partnership between TB Alliance and the Tropical Disease Foundation, Inc., will provide practical training, guidance, technical support, field experience, tools, and materials to national TB programs covering a wide range of topics including clinical management, diagnostics, drug safety monitoring, programmatic management, community engagement, and health economics. PeerLINC will continue to guide countries after completion of initial training, as countries work to implement and integrate the BPaL/M regimens into their national tuberculosis programs. The NC-009 trial, which launched in November 2023, will evaluate the safety and efficacy of a combination of a new experimental compound, TBAJ-876, with pretomanid and linezolid, components of the BPaL regimen. This new combination has the potential to shorten and improve treatment for both drug-sensitive and drug-resistant tuberculosis (TB). Results from preclinical and Phase 1 studies presented at the Union Conference showed that TBAJ-876, when compared to bedaquiline (an approved TB medicine in the same drug class), eliminated TB bacteria faster and had a potentially improved safety profile. "Australia has long been a leader in the global health community, and we greatly appreciate their unwavering support in the battle to end TB," said Dr. Mel Spigelman, President and CEO of TB Alliance. "This funding will contribute both to rapidly expanding access to improved treatments, and also to developing the next generation of even more effective TB cures. This award exemplifies the sort of global commitment and political will needed if we hope to, one day, end the TB pandemic." About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first designed and clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Prior to the initial BPaL clinical trial, less than one -third of drug-resistant TB patients around the world were being successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. 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, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jessica Wiggs, +1 (646) 616-8613 / [email protected] SOURCE TB Alliance

Phase 1Phase 2

16 Nov 2023

·www.prnewswire.com

TB Alliance Launches Five-Country Phase 2 Clinical Trial Evaluating Next-Generation TB Drug

Early results presented at the Union World Conference on Lung Health suggest promise of new compound to fight tuberculosis that will be tested as part of Phase 2 trial The first participant has been dosed in this partially double-blind study to evaluate the safety and efficacy of what has the potential to be a "universal regimen" to treat TB PARIS, Nov. 16, 2023 /PRNewswire/ -- TB Alliance launched a new Pan-Phase 2 clinical trial incorporating elements of Phase 2a, b and c, identified as NC-009, to evaluate the safety and efficacy of a combination of a new experimental compound, TBAJ-876, with pretomanid and linezolid, components of TB Alliance's BPaL regimen. This regimen has the potential to shorten and improve treatment for both drug-sensitive and drug-resistant tuberculosis (TB)—one of the world's deadliest infectious diseases. Results from preclinical and Phase 1 studies presented at the Union Conference showed that the new compound, when compared with bedaquiline (a TB medicine in the same drug class), eliminated TB bacteria faster and had a potentially safer profile. "A 'universal' TB medicine needs to be highly effective while causing very few adverse effects; initial Phase 1 trial results show that TBAJ-876 could possibly move the needle in this direction," said Dr. Mel Spigelman, President and CEO of TB Alliance. "If we can develop a regimen that is composed of novel compounds with minimal pre-existing resistance that is both highly potent and safe, it could blur the distinction between drug-sensitive and drug-resistant TB allowing for treatment of virtually all patients with active TB with the same regimen." The new trial, NC-009, will test different doses of TBAJ-876 in combination with pretomanid and linezolid against the current standard of care for drug-sensitive TB—isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE). Another arm of the trial will also test pretomanid and linezolid in combination with bedaquiline (BPaL), a regimen recommended by the World Health Organization to treat some forms of drug-resistant TB, against drug-sensitive TB. The study aims to enroll 300 participants with drug-sensitive TB at 21 clinical trial sites in five countries: Georgia, Philippines, South Africa, Tanzania, and Uganda. "To truly get ahead of the tuberculosis pandemic in all of its forms, we need to continually innovate," said Dr. Francesca Conradie, Principal Investigator for the NC-009 clinical trial in South Africa. "Recent innovations in drug-resistant TB therapy have been enormously important, but we need to continue to develop shorter, simpler, and more people-friendly cures, including in drug-sensitive TB where there hasn't been a new drug approved in more than 50 years." New Experimental Compound TBAJ-876 is a diarylquinoline, a category of antibiotic that targets a key enzyme of the tuberculosis bacteria involved in energy production. Bedaquiline, a TB drug approved for the treatment of drug-resistant TB by the US FDA in 2012, is in the same diarylquinoline drug class. At the Union Conference in Paris, data were presented—showing that the new experimental compound has the potential to become an important component in TB regimens moving forward: In in vitro studies, TBAJ-876 demonstrated anti-mycobacterial activity approximately 10-fold greater than bedaquiline. In mouse models of TB, TBAJ-876, together with pretomanid and linezolid, cured infections with shorter treatment durations than HRZE and BPaL regimens. TBAJ-876 also demonstrates greater activity against TB strains resistant to bedaquiline (Rv0678 mutants), suggesting it will also be more effective in treating these emerging strains. In preclinical studies, TBAJ-876 showed the potential to be safer than bedaquiline, including low potential for QT prolongation. In Phase 1 studies involving 165 healthy subjects, few, generally mild, adverse events were observed. About TB TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that all traces of the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. About BPaL The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. Previously, less than two-thirds of drug-resistant TB patients around the world had been successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9-20 months. 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, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany's Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Irish Aid, Korea International Cooperation Agency, National Institute of Allergy and Infectious Diseases, South Korea's Ministry of Foreign Affairs, Unitaid, and the United States Agency for International Development. For more information, please visit: . Contact: Jess Wiggs, [email protected], +1 240 425 7117 SOURCE TB Alliance

Phase 1Phase 2Drug ApprovalClinical Result

100 Deals associated with Pretomanid

External Link

KEGG	Wiki	ATC	Drug Bank
D10722	Pretomanid	J04	DB05154

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Multidrug resistant pulmonary tuberculosis	KR	Viatris, Inc.	15 Oct 2021
Tuberculosis, Multidrug-Resistant	NO	Mylan IRE Healthcare Ltd.	31 Jul 2020
Tuberculosis, Multidrug-Resistant	LI	Mylan IRE Healthcare Ltd.	31 Jul 2020
Tuberculosis, Multidrug-Resistant	EU	Mylan IRE Healthcare Ltd.	31 Jul 2020
Tuberculosis, Multidrug-Resistant	IS	Mylan IRE Healthcare Ltd.	31 Jul 2020
Extensively Drug-Resistant Tuberculosis	US	Mylan Ireland Ltd.	14 Aug 2019
Tuberculosis	US	Mylan Ireland Ltd.	14 Aug 2019

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Drug-Resistant Tuberculosis	NDA/BLA	CN	Mylan Laboratories Ltd.	12 Dec 2023
Drug-Resistant Tuberculosis	NDA/BLA	CN	Mylan Ireland Ltd.	12 Dec 2023
Drug-Resistant Tuberculosis	NDA/BLA	CN	Shenyang Hongqi Pharmaceutical Co., Ltd.	12 Dec 2023
Multidrug resistant pulmonary tuberculosis	Phase 2	GE	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	PH	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	ZA	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	TZ	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	ZM	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	KE	Global Alliance for TB Drug Development	01 Feb 2015
Multidrug resistant pulmonary tuberculosis	Phase 2	UG	Global Alliance for TB Drug Development	01 Feb 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02589782 (TB-PRACTECAL, Pubmed) Manual	Phase 2/3	Extensively Drug-Resistant Tuberculosis	552	standard care	rfbtxetleh(lzxbqonbng) = mfmwvcbexi grbtpagtuo (xsqhczjzle ) View more	Positive	01 Feb 2024
				BPaLM(bedaquiline + pretomanid + linezolid+ moxifloxacin )	rfbtxetleh(lzxbqonbng) = otjzdlhcmi grbtpagtuo (xsqhczjzle ) View more
NCT03338621 (CTgov)	Phase 2/3	Multidrug resistant pulmonary tuberculosis \| Tuberculosis, Multidrug-Resistant	455	ethambutol+rifampicin+isoniazid+pyrazinamide (Drug Sensitive-TB 2HRZE/4HR)	tzisewqwpy(hnjxkeihdv) = bnolekdpvs crkrsgoysx (mgvbmjcoyg, lyatuughwf - vkflrglgkb) View more	-	08 Nov 2023
				4BPaMZ (Drug Sensitive-TB 4BPaMZ)	tzisewqwpy(hnjxkeihdv) = jbmtpjyybc crkrsgoysx (mgvbmjcoyg, evdlchjxfs - pvqoqcuyoa) View more
NCT02256696 (CTgov)	Phase 2	Pulmonary Tuberculosis	157	PA-824+Rifampin+Isoniazid+Pyrazinamide (Arm 1)	qgwtxethum(ehfcfreykf) = fxaljahrxv smizqngkus (sohjuvlhml, gtweuwcsmp - uvyajannsl) View more	-	18 Jul 2023
				PA-824+Rifabutin+Isoniazid+Pyrazinamide (Arm 2)	qgwtxethum(ehfcfreykf) = gufqzfdxgq smizqngkus (sohjuvlhml, qhhimgipmg - sypiyjvadb) View more
NCT03086486 (ZeNix, CTgov)	Phase 3	Extensively Drug-Resistant Tuberculosis \| Pulmonary Tuberculosis \| Infectious Lung Disorder	181	Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200mg L x 26 Weeks + Pa + B)	fjhvnregzn(wfsnzpjtrw) = gtumvpthhs handvlomti (uypdkywdfo, gsgsfyzrbd - etwvtxrabc) View more	-	29 Jun 2023
				Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200 mg L x 9 Weeks + Pa + B)	fjhvnregzn(wfsnzpjtrw) = jbbljylntw handvlomti (uypdkywdfo, dzrhsoiuje - mtlvojwehd) View more
NCT02256696 (Pubmed \| Antimicrob Agents Chemother)	Phase 1	Tuberculosis	157	Pretomanid + Rifampin	ksntncxuvy(tmklquhhbc) = vjweejesbo egzgbltscg (jgjehfmmzx ) View more	-	20 Jan 2021
				Pretomanid + Rifabutin	ksntncxuvy(tmklquhhbc) = hhbvchbzhf egzgbltscg (jgjehfmmzx ) View more
NCT02333799 (Pubmed \| Br Dent J) Manual	Phase 3	Pulmonary Tuberculosis	109	bedaquiline+pretomanid+linezolid	tlqjqwexgn(umakvozxhs) = ldfynflugk rbkelevopc (mndqxdoujl ) View more	Positive	05 Mar 2020
NCT02333799 (Nix-TB, Pubmed)	Phase 3	Multidrug resistant pulmonary tuberculosis	109	Bedaquiline (B)	(vcbxgkuaiq) = zvcnsxcqwi nevkdsiovv (swndzbyvth ) View more	-	05 Mar 2020
				Pretomanid (Pa)	ifsazccios(yipmznxwgr) = hzcwbaitmz roxlolylig (bvaxjxzntl ) View more
NCT02193776 (NC-005, CTgov)	Phase 2	Pulmonary Tuberculosis	240	PA-824+Bedaquiline+Pyrazinamide (DS-TB: Bedaquiline (Loading Dose/t.i.w)+ PA-824 + Pyrazinamide)	ktfzfwybvk(swbrdrlsej) = cfvebvmcen rbzlnapdir (zuggrfbora, grgelbgxxg - lbcwtjqhcx) View more	-	26 Jul 2019
				PA-824+Bedaquiline+Pyrazinamide (DS-TB: Bedaquiline (200 mg) + PA-824 + Pyrazinamide)	ktfzfwybvk(swbrdrlsej) = iwnewuldpd rbzlnapdir (zuggrfbora, vrgajplrte - taykiwenqy) View more
NCT02342886 (STAND, CTgov)	Phase 3	Multidrug resistant pulmonary tuberculosis	284	PA-824+Moxifloxacin+Pyrazinamide (DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide)	ufokvkejhv(cgcsfikncr) = pobaxcprwl gundhsmozn (kikaewcows, jrgvrllxcq - krmbwpmtem) View more	-	26 Mar 2019
				PA-824+Moxifloxacin+Pyrazinamide (DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide)	ufokvkejhv(cgcsfikncr) = qyhhcurimw gundhsmozn (kikaewcows, ejcpfgokmm - wmraeokjng) View more
NCT00567840 (CTgov)	Phase 2	Pulmonary Tuberculosis	69	PA-824 (PA-824 200 mg)	kdoylxdqgs(pmzyrdrpbz) = kowuktyegq svwoytzdpn (kejhadklcl, bgkcntdazl - wpwxuzeshy) View more	-	04 Apr 2017
				PA-824 (PA-824 600 mg)	kdoylxdqgs(pmzyrdrpbz) = nvsaxtxjor svwoytzdpn (kejhadklcl, etbgkquftm - txboaigxfk) View more

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