- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard, Sutezolid (PNU-100480) / Sequella
Enrollment open, Trial initiation date: panTB-HM: A Pan-TB Regimen Targeting Host and Microbe (clinicaltrials.gov) - Aug 16, 2023
P2/3, N=352, Recruiting,
Initiation date: Apr 2023 --> Oct 2023 Not yet recruiting --> Recruiting | Initiation date: Jan 2023 --> Jul 2023
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: Favourable outcomes in RR-TB patients using BPaL and other WHO-recommended second-line anti-TB drugs. (Pubmed Central) - Jul 30, 2023
Overall, 66% of patients taking BPaL drugs as part of their background regimen had favourable treatment outcomes. Additionally, patients with RR-TB who were HIV-positive and taking HAART while receiving BPaL drugs as part of a background regimen had improved treatment outcomes.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Review, Journal: Tuberculosis in the European Region. (Pubmed Central) - Jun 26, 2023
TB control programs are facing emerging challenges that could change TB incidence in the near future. Novel antibiotic strategies and improved preventive policies could offer new opportunities to reduce the TB impact on public health.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Programmatic management of bedaquiline-pretomanid-linezolid regimens in Georgia. (Brown 3) - Jun 17, 2023 - Abstract #ERS2023ERS_854;
Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB. Endoscopy and interventional pulmonology; Public health; Imaging; Pulmonary function testing; General respiratory patient care; Respiratory intensive care; Epidemiology
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: Update of drug-resistant tuberculosis treatment guidelines: A turning point. (Pubmed Central) - Jun 5, 2023
The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded...The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all oral, more acceptable, equitable, and patient-centred model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Journal: Literature Highlights. (Pubmed Central) - May 30, 2023
Literature Highlights is a digest of notable papers recently published in the leading respiratory journals. Coverage includes clinical trials to investigate the diagnostic and clinical effect of trial of antibiotics on TB; a Phase 3 trial to assess if glucocorticoids decrease mortality among patients with pneumonia; a Phase 2 trial on pretomanid use for treating drug-susceptible TB; contact investigation for TB in China; and post-TB sequelae after TB treatment in children.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Journal: Fed- and Fasted-State Performance of Pretomanid Amorphous Solid Dispersions Formulated with an Enteric Polymer. (Pubmed Central) - May 23, 2023
These findings emphasize the limitations of in vitro assessment of ASD performance using standardized media conditions. Future studies are needed for improved understanding of food effects on ASD release and how this variability can be captured by in vitro testing methodologies for better prediction of in vivo outcomes, in particular for ASDs formulated with enteric polymers.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Journal: Pretomanid-Resistant Tuberculosis. (Pubmed Central) - May 1, 2023
The MAB_0540 mutation may be associated with resistance of M. abscessus to clofazimine. No abstract available
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Linezolid Resistance On the Rise In Drug Resistant Tuberculosis () - Apr 6, 2023 - Abstract #AFMRSER2023AFMR_SER_7;
With an MIC susceptibility breakpoint of 1.0 mg/L, TB strains are trending towards threatened resistance to linezolid. This is concerning as linezolid is essential in first-line regimens for the treatment of DRTB.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Increasing Fluoroquinolone Resistance In Drug Resistant TB () - Apr 6, 2023 - Abstract #AFMRSER2023AFMR_SER_6;
This is concerning as these agents are essential in first-line regimens for the treatment of DRTB. If the MICs continue to uptrend at a similar pace, we anticipate that more strains will surpass the breakpoint of 1 mg/L leading to potential ineffectiveness of both levofloxacin and moxifloxacin in the treatment of tuberculosis.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Journal: Promise and Peril of Pretomanid-Rifamycin Regimens for Drug-Susceptible Tuberculosis. (Pubmed Central) - Apr 4, 2023
If the MICs continue to uptrend at a similar pace, we anticipate that more strains will surpass the breakpoint of 1 mg/L leading to potential ineffectiveness of both levofloxacin and moxifloxacin in the treatment of tuberculosis. No abstract available
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: Update on drug treatments for multidrug resistant tuberculosis. (Pubmed Central) - Mar 15, 2023
The most expensive new antibiotic was pretomanid at $36 399 ( Although some concerns around safety and emergent bedaquiline resistance remain to be fully addressed, 6-month all oral regimens promise to transform the treatment of people with MDR-TB worldwide.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Cost-Effectiveness of Pretomanid-Based Regimen for Treatment of Highly Drug-Resistant Tuberculosis in a High-Income Country () - Mar 9, 2023 - Abstract #ISPOR2023ISPOR_1400;
OBJECTIVES: Treatment for highly resistant tuberculosis (HDR-TB) with bedaquiline-linezolid-based regimen is costly, takes a long time to complete, and has potentially life-threatening adverse effects. The BPaL therapy appeared to be effective in averting DALYs at reduced cost, with a high probability to be accepted as the preferred cost-effective option for HDR-TB treatment from the perspective of US healthcare provider.
- |||||||||| Journal: Designing molecular diagnostics for current tuberculosis drug regimens. (Pubmed Central) - Mar 2, 2023
P=N/A
Based on current knowledge, we also propose design priorities for next generation molecular assays to support triage of tuberculosis patients to appropriate and effective treatment regimens. We encourage assay developers to prioritize development of these key molecular assays and support the continued evolution, uptake, and utility of sequencing to build knowledge of tuberculosis resistance mechanisms and further inform rapid treatment decisions in order to curb resistance to critical drugs in current regimens and achieve End TB targets.Trial registration: ClinicalTrials.gov identifier: NCT05117788..
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Trial initiation date: Biodistribution and Pharmacokinetics of Pretomanid in Tuberculosis Patients Using 18F-Pretomanid PET (clinicaltrials.gov) - Feb 1, 2023
P=N/A, N=20, Recruiting,
These improvements to the overall TB regimen may improve access to the overall regimen by removing key cost-drivers, supply constraints, or manufacturing bottlenecks that plagued the previously disclosed routes. Initiation date: Nov 2022 --> Nov 2023
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Deltyba (delamanid) / Otsuka, Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: Mutations and insights into the molecular mechanisms of resistance of Mycobacterium tuberculosis to first-line. (Pubmed Central) - Feb 1, 2023
Additionally, understanding how and where mutations arise conferring a resistance profile to the bacteria and their effect on bacterial metabolism is an important requisite to be taken in producing safer and less susceptible drugs to the emergence of resistance. In this review, we summarize the most recent literature regarding novel mutations reported between 2017 and 2022 and the advances in the molecular mechanisms of action and resistance against first-line drugs used in tuberculosis treatment, highlighting recent findings in pyrazinamide resistance involving PanD and, additionally, resistance-conferring mutations for novel drugs such as bedaquiline, pretomanid, delamanid and linezolid.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard, Sutezolid (PNU-100480) / Sequella
New P2/3 trial: panTB-HM: A Pan-TB Regimen Targeting Host and Microbe (clinicaltrials.gov) - Jan 17, 2023
P2/3, N=352, Not yet recruiting,
- |||||||||| rifampicin / Generic mfg.
Review, Journal: Annual progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis in 2022 (Pubmed Central) - Jan 10, 2023
Meanwhile, different new chemotherapy regimens centered on new drugs have been explored in-depth by international scholars. In this article, we reviewed the progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis from October 2021 to September.
- |||||||||| linezolid oral / Generic mfg.
Preclinical, Journal: Efficacy of Replacing Linezolid with OTB-658 in Anti-Tuberculosis Regimens in Murine Models. (Pubmed Central) - Jan 10, 2023
A newly approved regimen combining LZD with bedaquiline (BDQ) and pretomanid (PMD) (BPaL regimen) is the first 6-month oral regimen that is effective against multidrug- and extensively drug-resistant tuberculosis...In BALB/c mice, replacing 100 mg/kg LZD with 100 mg/kg OTB-658 in the TBI-166 + BDQ backbone resulted in no culture-positive lungs at 4 and 8 weeks of treatment, and there were no significant differences in relapses rate between the groups. In conclusion, OTB-658 is a promising clinical candidate that could replace LZD in the BPaL or TBI-166 + BDQ + LZD regimens and should be studied further in clinical trials.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development
Preclinical, Journal: Dynamic F-Pretomanid PET imaging in animal models of TB meningitis and human studies. (Pubmed Central) - Dec 30, 2022
Finally, first-in-human dynamic F-pretomanid PET in six healthy volunteers demonstrates excellent CNS penetration of pretomanid, with significantly higher levels in the brain parenchyma than in CSF. These data have important implications for developing new antibiotic treatments for TB meningitis.
- |||||||||| pretomanid (PA-824) / Global Alliance for TB Drug Development, Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. (Pubmed Central) - Dec 23, 2022
P2/3
In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782.).
- |||||||||| Review, Journal: New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians. (Pubmed Central) - Dec 16, 2022
This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development.
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