The Pathway to Potential New TB Treatments

Pretomanid is the result of years of scientific research and development enabled by the essential support of TB Alliance’s donors and other stakeholders.

Over the years, pretomanid has been studied in 19 clinical trials in 14 countries with more than 1,100 clinical trial participants. Learn about the history of pretomanid, and where we stand today.

  • FDA Approval

    Pretomanid received approval from the U.S. Food and Drug Administraion (FDA) for the use of pretomanid for the treatment of highly drug-resistant TB in a combination regimen
  • FDA Advisory Committee

    FDA Antimicrobial Drugs Advisory Committee votes 14-4 in favor of safety and efficacy of pretomanid for use in the BPaL regimen
  • Marketing Authorization Application (MAA) submitted

    MAA submitted to European Medicines Agency for pretomanid, in combination with bedaquiline and linezolid
  • New Drug Application (NDA) filed

    NDA accepted for FDA Priority Review for pretomanid, in combination with bedaquiline and linezolid for the treatment of extensively drug-resistant TB (XDR-TB) and treatment-intolerant or non-responsive multidrug-resistant TB (MDR-TB)
  • NDA submitted

    NDA submitted to FDA for pretomanid, in combination with bedaquiline and linezolid for the treatment of XDR-TB and treatment-intolerant or non-responsive MDR-TB
  • Interim Nix-TB data presented

    Data from Nix-TB trial presented at Union Conference, showing among first 75 XDR-TB patients, BPaL regimen cured 89% after six months of treatment and six months of post-treatment follow-up
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  • ZeNix continues study of BPaL

    ZeNix Phase 3 clinical trial begins, aiming to optimize BPaL
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  • Nix-TB begins enrollment

    Phase 3 Nix-TB clinical trial of BPaL regimen begins, evaluating the most drug-resistant forms of TB, including XDR-TB
  • First Phase 3 begins

    Launch of first Phase 3 trial including Pretomanid
  • Advancing new regimens

    Pretomanid Phase 2B clinical trial begins
  • Non-proprietary name for pretomanid accepted

    In a nod to TB Alliance research center in Pretoria, South Africa, Pretomanid becomes new non-proprietary name for PA-824
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  • Salvage study proposed

    Concept for first new study of a novel, all-oral regimen for the most resistant TB cases led to the initiation of the Nix-TB clinical trial
  • Phase 2B begins

    PaMZ Phase 2B clinical trial begins
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  • First trial to test new TB regimen

    Pretomanid (PA-824) included in first clinical trial to test combination (PaMZ) of multiple new TB drugs
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  • Phase 2 begins

    Phase 2 early bactericidal activity clinical trial begins for pretomanid (PA-824)
  • First-ever "combo study"

    TBA launches preclinical combination study — the first of its kind in TB
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  • Phase 1 begins

    Pretomanid (PA-824) Phase 1 clinical trial begins
  • Investigational New Drug application filed

    TB Alliance submits an Investigational New Drug application for pretomanid (PA-824)
  • Preclinical Development

    Pretomanid (PA-824) preclinical studies begin
  • PA-824 in-licensed

    TB Alliance in-licenses pretomanid (PA-824) and analogs from Chiron
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  • New compound shows potential

    Nature article mentions the promise of pretomanid (PA-824) to treat TB based on preclinical data
 

INDICATION | LIMITED POPULATION

Pretomanid Tablet is an antimycobacterial indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug-resistant (XDR), treatment-intolerant or non-responsive multidrug-resistant (MDR) tuberculosis (TB). Approval of this indication is based on limited clinical safety and efficacy data. This drug is indicated for use in a limited and specific population of patients.

Limitations of Use:
  • Pretomanid Tablets are not indicated for patients with:
    • Drug-sensitive (DS) tuberculosis
    • Latent infection due to Mycobacterium tuberculosis
    • Extra-pulmonary infection due to Mycobacterium tuberculosis
    • MDR-TB that is not treatment-intolerant or non-responsive to standard therapy
  • Safety and effectiveness of Pretomanid Tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen.

IMPORTANT SAFETY INFORMATION

Contraindications

Pretomanid Tablets used in combination with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid is contraindicated.

Warnings and Precautions
  • Hepatic adverse reactions were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor symptoms and signs and liver related laboratory tests. Interrupt treatment with the entire regimen if evidence of liver injury occurs.
  • Myelosuppression was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor complete blood counts. Decrease or interrupt linezolid dosing if significant myelosuppression develops or worsens.
  • Peripheral and optic neuropathy were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor visual function. Obtain an ophthalmologic evaluation if there are symptoms of visual impairment. Decrease or interrupt linezolid dosing if neuropathy develops or worsens.
  • QT prolongation was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops.
  • Reproductive effects: Pretomanid caused testicular atrophy and impaired fertility in male rats. Advise patients of reproductive toxicities seen in animal studies and that the potential effects on human male fertility have not been adequately evaluated.
  • Lactic acidosis was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Consider interrupting linezolid or the entire combination regimen of Pretomanid Tablets, bedaquiline, and linezolid dosing if significant lactic acidosis develops.

Adverse Reactions

The most common adverse reactions (≥10%) are peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased transaminases, dyspepsia, decreased appetite, rash, pruritus, abdominal pain, pleuritic pain, increased gamma-glutamyltransferase, lower respiratory tract infection, hyperamylasemia, hemoptysis, back pain, cough, visual impairment, hypoglycemia, abnormal loss of weight, and diarrhea.