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pretomanid

Trade name: pretomanid

Small moleculeapprovedOrphan Drug FDAFast Track FDA

Approved

Aug 14, 2019

Pretomanid (PA-824) is an experimental anti-tuberculosis drug. Pretomanid is a bicyclic nitroimidazole-like molecule with a very complex mechanism of action. It is active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis. As a potential TB therapy, it has many attractive characteristics - most notably its novel mechanism of action, its activity in vitro against all tested drug-resistant clinical isolates, and its activity as both a potent bactericidal and a sterilizing agent in mice. In addition, the compound shows no evidence of mutagenicity in a standard battery of genotoxicity studies, no significant cytochrome P450 interactions, and no significant activity against a broad range of Gram-positive and Gram-negative bacteria. This compound has been developed by TB Alliance and is a potential cornerstone of future TB and drug-resistant TB treatment regimens. It is currently undergoing Phase III clinical trials. — NCATS

Clinical trial activity

39 trials · 88 clinical orgs · 2 marketing orgs

Phase 1
11
Phase 2
20
Phase 3
11
Phase 4
2

Earliest trial started Mar 1, 2003 (NCT00042289)

Timeline

2000s

  1. Jan 1, 2006

    Global Alliance for TB Drug Development — Earliest Phase 1 Sponsor(trial)

  2. Jan 1, 2007

    Global Alliance for TB Drug Development — Earliest Phase 2 Sponsor(trial)

  3. Jul 5, 2007

    Orphan Drug Designation

2010s

  1. Jan 1, 2015

    Global Alliance for TB Drug Development — Earliest Phase 3 Sponsor(trial)

  2. Aug 14, 2019

    Global Alliance for TB Drug Development — Earliest FDA Approval

  3. Aug 14, 2019

    Mylan — Marketing Organization

  4. Aug 14, 2019

    Global Alliance for TB Drug Development — NDA Organization

  5. Aug 14, 2019

    Mylan — NDA Secondary Org

Indications

Approved for

Studied for

Mechanism of action

  • Inducible nitric oxide synthaseINHIBITOR

    Inducible nitric oxide synthase inhibitor

  • Unspecified targetOTHER

    Unknown

    Antimycobacterial. Potentially a dual mechanism, the molecular target is not fully elucidated. In the bacterial cell, pretomanid undergoes nitro-reduction catalysed by the bacterial enyzyme Ddn. The nitro-reduction step is dependent on the reduced cofactor F420 which is produced by the bacterial enzyme Fgd1. Under aerobic conditions, in actively respiring bacteria, the active compound is proposed to inhibit mycolic acid biosynthesis. Under anaerobic conditions, in non-respiring bacteria, the NO released by Ddn processing is proposed to act as a respiratory poison. Alternatively, it has been suggested that both active and non-respiring bacteria are targeted through disrupted sugar phosphate metabolism and toxic methylglyoxal accumulation.

Approval history

  • approvedPriority reviewFast trackAug 14, 2019

Chemistry & pharmacology

Loading structure…

SMILES

[O-][N+](=O)C1=CN2C[C@@H](COC2=N1)OCC3=CC=C(OC(F)(F)F)C=C3
Mol. weight
359.2574 g/mol
Lipinski Ro5
Pass
Rule of 3
No
Chirality
Single Stereoisomer
Inorganic
No
Polymer
No
Delivery
Oral
Availability
Prescription Only

Oral

Yes

Parenteral

No

Topical

No

First in class

Sources

Also known as

  • 2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5h-imidazo(2,1-b)(1,3)oxazine
  • pa 824
  • pa-824
  • pa-824
  • pa-824
  • pa-824
  • pa824 cpd
  • pretomanid
  • pretomanid
  • pretomanid
  • pretomanid
  • pretomanid

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT07227779Phase 2Feb 15, 2026Makerere University, University of Minnesota
NCT07126639N/ASep 1, 2025Huazhong University of Science and Technology
NCT06798675Phase 2Aug 31, 2025nephCentric
NCT06905522Phase 3Apr 15, 2025Shenyang Tenth People's Hospital, Shenzhen Third People's Hospital, Zhejiang University
NCT06441006Phase 3Nov 1, 2024Johns Hopkins University, University of California, San Francisco
NCT06192160Phase 2Oct 15, 2024National Institute of Allergy and Infectious Diseases (NIAID), TB Alliance, University of California, Berkeley, Vanderbilt University
NCT06114628Phase 2Dec 8, 2023German Center for Infection Research, GlaxoSmithKline, Government of France, Janssen Pharmaceutica NV, KNCV Tuberculosis Foundation, Otsuka, Radboud University, Research Center Borstel, TASK Applied Science, TB Alliance, Tuberculosis Network European Trialsgroup, University of California, San Francisco, University of Cambridge, University of Hamburg, University of Liverpool, University of London, University of Milan, University of Oxford, University of Porto, University of St Andrews, Uppsala University, Vita-Salute University of Milano. Italy
NCT06058299Phase 2Oct 31, 2023Global Alliance for TB Drug Development, TB Alliance
NCT05686356Phase 2/Phase 3 (Phase 3)Jul 28, 2023Aurum Institute, Global Alliance for TB Drug Development, Government of Mozambique, Katholieke Universiteit Leuven, Ludwig Maximilians University, National Institute for Medical Research, Tanzania, Sequella, Inc., Stellenbosch University, Wits Health Consortium (Pty) Ltd
NCT05971602Phase 2Jul 26, 2023Bill and Melinda Gates Foundation, Global Alliance for TB Drug Development, Janssen Pharmaceutica NV, Otsuka
NCT05586230Phase 1Feb 28, 2023Global Alliance for TB Drug Development, Johns Hopkins University, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
NCT05381194Phase 4Dec 13, 2022Catholic University of Korea, Chonbuk National University, Chonnam National University, Dongguk University, Incheon St.Mary's Hospital, Pusan National University, Seoul National University, Soon Chun Hyang University, Sungkyunkwan University, University of Ulsan, Yonsei University
NCT05040126Phase 3Oct 7, 2021B. J. Medical College and Hospital, Govt. Medical College, Surat, King George's Medical University, National Institute for Research in Tuberculosis, Chennai, India, Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, Sarvodaya Charitable Trust Hospital, Ghatkopar, Mumbai, Shatabdi Centenary Hospital, Govandi, Mumbai, SN Medical College, Agra, The international Union Against Tuberculosis and Lung Diseases, Paris
NCT04179500Phase 1Apr 30, 2020Global Alliance for TB Drug Development
NCT04207112Phase 2/Phase 3 (Phase 3)Jan 31, 2020Government of Belarus, Government of Uzbekistan, Medecins Sans Frontieres, TB & HIV Investigative Network (THINK), University of Liverpool, University of London, Wits Health Consortium (Pty) Ltd
NCT04309656Phase 1Jan 14, 2020Global Alliance for TB Drug Development, World Wide Clinical Trials Early Phase Services, LLC
NCT04081077Phase 2/Phase 3 (Phase 3)Oct 1, 2019Drugs for Neglected Diseases Initiative, ERT Clinical, Global Alliance for TB Drug Development, Government of Belarus, Government of Uzbekistan, Hackensack University Medical Center, Medecins Sans Frontieres, Republican Research and Practical Centre for Pulmonology and Tuberculosis, TB & HIV Investigative Network (THINK), University of Basel, University of California, San Francisco, University of Liverpool, University of London, Wits Health Consortium (Pty) Ltd, World Health Organization
NCT03942354Phase 2/Phase 3 (Phase 3)Jul 1, 2019Don McKenzie Hospitals, Kwazulu Natal, South Africa, Doris Goodwin Hospitals, Kwazulu Natal, South Africa, Medecins Sans Frontieres, Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital, Republican specialised scientific-practical medical centre, Tashkent, Republican TB Hospital No. 2, Nukus, University of London, University of Sussex
NCT03896750Phase 1May 9, 2019National Institute of Allergy and Infectious Diseases (NIAID)
NCT03338621Phase 2Jul 30, 2018Global Alliance for TB Drug Development
Showing 20 of 39 trials
Page 1 / 2

Organizations

Research & Development (88)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
Global Alliance for TB Drug DevelopmentAcademic/Hospital221732006
National Institute of Allergy and Infectious Diseases (NIAID)Government7732003
University of LondonAcademic/Hospital5122017
Johns Hopkins UniversityAcademic/Hospital4132012
Medecins Sans FrontieresAcademic/Hospital4412017
University of Cape TownAcademic/Hospital4012007
Government of BelarusGovernment3012017
Government of UzbekistanGovernment3012017
Karl Bremer Hospital, Cape Town South AfricaAcademic/Hospital3012009
MDS PharmaFor profit3012007
TB AllianceAcademic/Hospital3012023
TB & HIV Investigative Network (THINK)Academic/Hospital3012017
University of California, San FranciscoAcademic/Hospital3122019
University of LiverpoolAcademic/Hospital3022019
Wits Health Consortium (Pty) LtdAcademic/Hospital3012019
Drugs for Neglected Diseases InitiativeAcademic/Hospital2012017
ERT ClinicalFor profit2012017
Janssen Pharmaceutica NVFor profit2012023
National Institutes of Health (NIH)Government2022003
OtsukaFor profit2012023
88 organizations
Page 1 / 5

Marketing (3)

OrganizationOrg typeRelationshipDate
Global Alliance for TB Drug DevelopmentAcademic/HospitalNDAAug 14, 2019
MylanFor profitMKTGAug 14, 2019
MylanFor profitNDA2Aug 14, 2019