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

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

The Struggle to End a Millennia-Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis. (PubMed, Drugs) - "An extensive review of the efficacy and safety data for key contemporary drugs already incorporated into treatment regimens, such as bedaquiline, pretomanid, and linezolid, is provided...Amongst others, the highly optimistic and potent anti-mycobacterial activity of agents such as BTZ-043, PBTZ 169, and OPC-167832 are emphasized. The evolving spectrum of oxazolidinones, such as sutezolid, delpazolid, and TBI-223, all aiming to exceed the efficacy achieved with linezolid yet offer a safer alternative to the potential toxicity, are reviewed. New and exciting prospective agents with novel mechanisms of impact against TB, including 3-aminomethyl benzoxaboroles and telacebec, are underscored. We describe new diaryloquinolines in development, striving to build on the immense success of bedaquiline. Finally, we discuss some of these compounds that have shown encouraging additive or synergistic benefit when used in combination, providing some promise for the future in treating..."

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

PanACEA DElpazolid Dose-finding and COmbination DEvelopment (DECODE) (clinicaltrials.gov) - P2b | N=76 | Active, not recruiting | Sponsor: LegoChem Biosciences, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Mar 2024 | Trial primary completion date: May 2022 ➔ Dec 2023

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Long-Term Treatment with Delpazolid Alone and in Combination with Bedaquiline and Delaminid in a Murine Tuberculosis Model (ASM Microbe 2022) - "The goal of this study was to evaluate the activity of DPZ combined with bedaquiline (BDQ) and delamanid (DLM) compared to LZD/BDQ/DLM in a long-term murine tuberculosis model... DPZ may be an excellent replacement for LZD due to fewer side effects and its ability to enhance treatment results when combined with other drugs potentially included in MDRTB therapy."

Combination therapy • Preclinical • 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) - P2a | N=100 | Recruiting | Sponsor: LegoChem Biosciences, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy

A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia (clinicaltrials.gov) - P2a | N=100 | Not yet recruiting | Sponsor: LegoChem Biosciences, Inc

Monotherapy • New P2a trial

An Overview of Bioactive 1,3-Oxazole-Containing Alkaloids from Marine Organisms. (PubMed, Pharmaceuticals (Basel)) - "These alkaloids have attracted extensive attention from medicinal chemists and pharmacologists owing to their diverse arrays of chemical structures and biological activities, and a series of 1,3-oxazole derivatives has been developed into therapeutic agents (e.g., almoxatone, befloxatone, cabotegravir, delpazolid, fenpipalone, haloxazolam, inavolisib). To improve our knowledge regarding these marine-derived substances, as many as 285 compounds are summarized in this review, which, for the first time, highlights their sources, structural features and biological properties, as well as their biosynthesis and chemical synthesis. Perspective for the future discovery of new 1,3-oxazole compounds from marine organisms is also provided."

Journal • Review

Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis. (PubMed, Antimicrob Agents Chemother) - P2 | "Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483."

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