delpazolid (LCB01-0371) / LigaChem Biosci, HaiHe Biopharma - LARVOL DELTA

Synergistic activity of fosfomycin combined with old and new oxazolidinones (linezolid, contezolid, delpazolid, and sutezolid) against bloodstream isolates of vancomycin-resistant Enterococcus faecium. (PubMed, Eur J Clin Microbiol Infect Dis) - "Our findings provide preclinical evidence supporting the use of fosfomycin in combination with novel oxazolidinones as a promising therapeutic strategy against VR E. faecium infections."

Journal • Infectious Disease

Updates in the clinical management of Tuberculous meningitis. (PubMed, Expert Rev Anti Infect Ther) - "Emphasis is placed on high-dose rifampicin, linezolid, and novel oxazolidinones such as sutezolid and delpazolid...Steroids like dexamethasone are already used, while drugs like aspirin and thalidomide are being studied. Children, pregnant women, and people with HIV are at special risk and need extra care. With faster tests, stronger drugs, and safer treatment plans, there is new hope that more people will survive and recover well."

Journal • Review • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis • Vascular Neurology

PanACEA - STEP2C -01 (clinicaltrials.gov) - P2 | N=390 | Recruiting | Sponsor: Michael Hoelscher | N=270 ➔ 390 | Trial completion date: Feb 2025 ➔ Dec 2027 | Trial primary completion date: Feb 2025 ➔ Oct 2027

Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomised, open-label, phase 2b, dose-finding trial. (PubMed, Lancet Infect Dis) - P2 | "The pharmacokinetic-pharmacodynamic modelling results suggest that delpazolid adds efficacy on top of bedaquiline, delamanid, and moxifloxacin; and that a dose of 1200 mg once daily would result in exposures with maximum efficacy. That dose was shown to be safe, raising hope that linezolid toxicities could be averted in long-term treatment. Delpazolid is a promising drug for future tuberculosis treatment regimens and could be widely usable if safety and efficacy are confirmed in larger trials."

Journal • P2b data • Gastrointestinal Disorder • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Leukopenia • Neutropenia • Optic Neuritis • Pain • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Tuberculosis

Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: LigaChem Biosciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Cardiac safety of bedaquiline, delamanid and moxifloxacin co-administered with or without varying doses of sutezolid or delpazolid for the treatment of drug-susceptible TB. (PubMed, J Antimicrob Chemother) - "The drug regimens containing standard doses of bedaquiline, delamanid and moxifloxacin, and varying doses of sutezolid or delpazolid were not found to pose a high cardiac risk in a population without further QTc-relevant risk factors. However, close monitoring of the QTc interval remains essential in patients with TB treated with combination drug therapy with known QTc-prolonging drugs."

Journal • Cardiovascular

Establishing Structure-Activity Relationships in Heterogeneous Catalysis of Three-Component Organic Coupling Reactions by Lewis Acidic Metal Sites and Polar Moieties. (PubMed, ACS Appl Mater Interfaces) - "A wide spectrum of substrates with diverse electronic, steric, and polarizing effects is tested to obtain bioactive precursors, particularly tedizolid and delpazolid, achieving high conversion rates (65-94%) and turnover numbers. The postcatalysis analysis of both Co-bpaipa and Ni-bpaipa demonstrates their structural stability and nonleachability, even after multiple catalytic runs."

Heterogeneity • Journal

Comparative In Vitro Drug Susceptibility Study of Five Oxazolidinones Against Mycobacterium tuberculosis in Hainan, China. (PubMed, Pathogens) - "In this study, we aimed to compare the in vitro activity of linezolid (LZD) and four oxazolidinones, including tedizolid (TZD), contezolid (CZD), sutezolid (SZD), and delpazolid (DZD), against multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) isolates from Hainan. In vitro susceptibility testing indicated that SZD exhibited the strongest antibacterial activity, followed by TZD and LZD, while CZD and DZD demonstrated comparable but weaker effectiveness. Mutations in rplD and mce3R were discovered, but further research is needed to clarify their role in conferring oxazolidinone resistance in MTB."

Clinical • Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Comparative pharmacokinetics study of two tablet formulations of delpazolid, a novel oxazolidinone class antibiotic. (PubMed, Transl Clin Pharmacol) - P1 | "The two different delpazolid formulations showed comparable PK and safety profiles, indicating that the test drug is an appropriate alternative to the reference drug. ClinicalTrials.gov Identifier: NCT04939779."

Journal • PK/PD data • Infectious Disease

Management of Refractory Nontuberculous Mycobacterial Pulmonary Disease (KATRDIC 2024) - "Liposomal amikacin, for example, has shown an additional 20% bacterial conversion in refractory cases. Other new drugs, such as epetraborole, delpazolid, inhaled clofazimine, and omadacycline, have also been utilized for NTM-PD. When bacterial conversion is difficult, the treatment goal may shift to improving quality of life through appropriate antibiotic therapy. This presentation will comprehensively address the causes of treatment-refractory NTM-PD and outline appropriate management strategies."

Nontuberculous mycobacteria • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: LigaChem Biosciences, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon? (PubMed, Pharmaceutics) - "The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia (clinicaltrials.gov) - P2 | N=40 | Terminated | Sponsor: LigaChem Biosciences, Inc. | N=100 ➔ 40 | Trial completion date: Nov 2024 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Feb 2024; Early termination; Difficulties in enrolling subjects due to the decrease in patients with MRSA bacteremia

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination

Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01-0371) in Adult Patients with Pulmonary Tuberculosis. (PubMed, J Clin Pharmacol) - "The PK-PD simulation suggested that the bacterial titers are the lowest on the 800 mg bid regimen among the four, consistent with observed data, as all regimens substantially decrease. In the dose-response relationship, the effectiveness of delpazolid was suggested."

Journal • PK/PD data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

PanACEA DElpazolid Dose-finding and COmbination DEvelopment (DECODE) (clinicaltrials.gov) - P2 | N=76 | Completed | Sponsor: LegoChem Biosciences, Inc | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2 | Trial completion date: Mar 2024 ➔ Sep 2023

Phase classification • Trial completion • Trial completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: LegoChem Biosciences, Inc | Not yet recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P2

Enrollment closed • Phase classification • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: LegoChem Biosciences, Inc | Phase classification: P2a ➔ P2 | Trial completion date: Nov 2023 ➔ Nov 2024 | Trial primary completion date: Nov 2023 ➔ Nov 2024

Monotherapy • Phase classification • Trial completion date • Trial primary completion date

Intracellular and in vivo activities of oxazolidinone drugs against Mycobacterium avium complex infection. (PubMed, Sci Rep) - "The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited success, highlighting the need for better therapeutic strategies...Here, we first evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC strains and one macrolide-resistant M. avium strain in murine bone marrow-derived macrophages (BMDMs) and found that both drugs demonstrated similar potential...Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs exhibited no anti-MAC effect, and there was no significant difference in the synergistic effect of CLR between LZD and DZD. These findings suggest that oxazolidinone drugs inhibit intracellular bacterial growth, even against macrolide-resistant MAC, but their clinical..."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex (clinicaltrials.gov) - P2a | N=20 | Not yet recruiting | Sponsor: LegoChem Biosciences, Inc | Phase classification: P2 ➔ P2a

Phase classification • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Study to Evaluate the Efficacy of Delpazolid as Add-on Therapy in Refractory Mycobacterium Abscessus Complex (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: LegoChem Biosciences, Inc

New P2 trial • New P2a trial • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. (PubMed, Trials) - P2b | "DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages."

Combination therapy • Journal • P2b data • PK/PD data • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis

In-vitro Activity of Delpazolid and Comparator Agents Against Methicillin-resistant Staphylococcus aureus Involved in Bloodstream Infection. (PubMed, Ann Lab Med) - No abstract available

Journal • Preclinical • Infectious Disease

Antimicrobial Effect of Oxazolidinones and Its Synergistic Effect with Bedaquiline Against Mycobacterium abscessus Complex. (PubMed, Infect Drug Resist) - "The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections."

Journal • Infectious Disease

Annual progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis in 2022 (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "New chemotherapeutic drugs such as delpazolid, sutezolid, telacebec and independently developed anti-tuberculosis drugs such as pyrifazimine, sudapyridine and JBD0131 are still in clinical trials. The efficacy, safety, tolerability, adverse reactions and drug resistance of bedaquiline, linezolid, delamanid and pretomanid have been studied extensively. 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."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Novel oxazolidinones harbor potent in vitro activity against the clinical isolates of multidrug-resistant Mycobacterium tuberculosis in China. (PubMed, Front Med (Lausanne)) - "The minimum inhibitory concentrations (MICs) of linezolid, tedizolid, sutezolid, delpazolid, and contezolid against 16 mycobacterial reference strains and 69 M. tuberculosis clinical isolates, including 17 drug-susceptible isolates and 52 multidrug-resistant (MDR) isolates, were determined by microplate alamarBlue assay (MABA). Different oxazolidinones can have discrepant antimicrobial activity against different mycobacterial species, or have different manifestations out of cell or in cell. Understanding these differences would be helpful in choosing the appropriate drug in clinical practice."

Journal • Preclinical • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis