Pretomanide

Pretomanid is a prodrug that is activated in the body and inhibits the formation of mycolic acid, an important component of tuberculosis bacteria. Pretomanid was developed against resistant tuberculosis (TB). It was approved in Europe in 2020. Despite approval and positive recommendations by the WHO, access for patients in Europe (and therefore also in Germany) remains limited. Efforts are underway to extend approval and facilitate access, as the drug is an important option for the treatment of multidrug-resistant TB (MDR-TB).

Pretomanid is used in combination with other drugs(bedaquiline and linezolid) to treat MDR-TB, especially if other therapies do not work or are not tolerated.

Although Pretomanid is approved in Europe, Pretomanid is not commercially available in Germany. Pretomanid is currently only approved by the EMA in combination with bedaquiline and linezolid (BPaL regimen) and is restricted to extensively drug-resistant (XDR) and selected MDR-TB patients.

In patients with uncomplicated rifampicin-resistant tuberculosis treated with pretomanid-moxifloxacin-pyrazinamide, 91% (95% CI 59-100) had favorable treatment outcomes at the end of treatment. In patients with highly resistant tuberculosis, 90% (95% CI 83-95) had favorable outcomes with pretomanid-bedaquiline-linezolid six months after treatment, but linezolid-related toxicities were common. No acquired resistance to pretomanid has been reported (Gils T et al. 2022).

However, data from recent clinical trials show the efficacy of an extended regimen consisting of BPaL plus moxifloxacin (BPaLM) as a new standard of care for MDR/RR-TB (Conradie F et al. 2022). This emerges, for example, from the "TB-PRACTECAL" study published in The Lancet Respiratory Medicine in 2024 (Nyang'wa BT et al. 2024).

Costs and reimbursement: The German hospital financing system (G-DRG) and the lack of a corresponding code make it difficult to integrate and reimburse the drug, as the case numbers are too low to collect meaningful cost data.

Current developments(WHO recommendations): The World Health Organization (WHO) has recommended the use of shortened treatment regimens containing pretomanid from 2022.

Changes to the WHO guidelines: In April 2025, the WHO recommendations were updated to include treatment options without Pretomanid, which are also costly.

DZK-Initiative (Deutsche Zentrale Tuberkulose-Hilfe):The Deutsche Zentrale Tuberkulose-Hilfe (DZK) is working on position papers to comment on the new recommendations and support access to the different regimens available.

1. Conradie F et al. (2022) Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med 387:810-823.
2. Gils T et al. (2022) Pretomanid for tuberculosis: a systematic review. Clin Microbiol Infect 28:31-42.
3. Kadura S et al. (2020) Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid. J Antimicrob Chemother 75:2031-2043.
4. Nyang'wa BT et al. (2024) Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomized, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med 12:117-128.