sudapyridine (WX-081) / Guangzhou JOYO Pharma - LARVOL DELTA

Catalytic enantioselective total synthesis of antitubercular agents (-)-bedaquiline and (-)-sudapyridine enabled by dynamic kinetic resolution-asymmetric transfer hydrogenation. (PubMed, Chem Sci) - "Furthermore, the aforementioned two-stage protocol has been successfully applied to the synthesis of (-)-sudapyridine, a tuberculosis drug candidate currently in phase III clinical trials. This study presents a versatile and generalizable strategy for the synthesis of BDQ-type architectures, which hold significant interest for both medicinal and process chemists."

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

Population pharmacokinetic and exposure-response study of a novel anti-tuberculosis drug to inform its dosage design in phase III clinical trial. (PubMed, Eur J Pharm Sci) - "Although bedaquiline (BDQ) received conditional approval for multi-drug resistance tuberculosis (MDR-TB), a black box warning was added due to QT prolongation risk. According to the simulation results of different regimens, the dosage of 450 mg once daily (QD) for 1 week and subsequent 300 mg QD for 1 week followed by 150 mg QD for 22 weeks was recommended considering both efficacy and safety. Our study revealed the PK and efficacy profiles of WX-081 for the first time and proposed a dose optimization strategy to facilitate its clinical development."

Journal • P3 data • PK/PD data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

In vitro and in vivo antibacterial activity of sudapyridine (WX-081) combined with other drugs against Mycobacterium abscessus. (PubMed, Tuberculosis (Edinb)) - "The objective of this study was to investigate the in vitro, intracellular, and in vivo antibacterial activity of sudapyridine (WX-081) in combination with clarithromycin (CLR), clofazimine (CFZ), rifabutin (RFB), and linezolid (LZD) against MAB. In vivo studies demonstrated that the combination of WX-081 with CLR or both CLR and CFZ displayed antibacterial activity and significantly prevented mouse mortality. Our study demonstrates that the concurrent use of WX-081 with CLR or CLR plus CFZ holds significant promise as a clinical intervention for MAB infection."

Journal • Preclinical • Infectious Disease

Evaluation of the Drug Interaction Study and Food Effects Study of WX-081 Tablets with Itraconazole and Rifampicin in Chinese Adult Healthy Volunteers (ChiCTR) - P1 | N=48 | Recruiting | Sponsor: The First Hospital of Jilin University; The First Hospital of Jilin University

New P1 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Sudapyridine (WX-081) inhibits Mycobacterium tuberculosis by targeting ATP synthase and upregulating host innate immunity. (PubMed, mSphere) - "Molecular docking confirmed atpE binding sites, and immune activation pathways (NF-κB/MAPK) were identified, positioning WX-081 as a potent, safe anti-DR-TB candidate despite unresolved mechanistic details.IMPORTANCEBedaquiline, a key drug for drug-resistant tuberculosis, is restricted by safety issues impacting its clinical utility. Its next-generation alternative, WX-081, has advanced to Phase III trials but lacks in-depth studies on its mechanism and host immune-modulatory effects, necessitating further research before broad clinical adoption."

Journal • Cardiovascular • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

WX081-DDI: Drug-Drug Interaction and Food Effect of Sudapyridine(WX-081) With Itraconazole and Rifampin in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd | Initiation date: Dec 2024 ➔ May 2025 | Trial primary completion date: Feb 2025 ➔ Oct 2025

Trial initiation date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Therapeutic Strategies for Tuberculosis: Progress and Lessons Learned. (PubMed, Biomed Environ Sci) - "Promising agents such as second-generation bedaquiline analogs (TBAJ-587, TBAJ-876), sudapyridine (WX-081), delamanid, pretomanid, and TBI-166 (pyrifazimine) have shown efficacy against resistant Mtb strains...Agents such as vitamin D, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin, and biological agents like interleukins and granulocyte-macrophage colony-stimulating factor are under exploration...Despite these advancements, significant challenges remain in achieving the World Health Organization's "End TB Strategy" goals, particularly as the COVID-19 pandemic has diverted resources and attention. Ongoing research and global collaboration are crucial to develop novel therapeutic strategies, optimize treatment regimens, and ultimately reduce the global burden of TB."

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

WISH: A Phase III Study of Oral Sudapyridine (WX-081) Tablets in Rifampicin-Resistant Pulmonary Tuberculosis Patients (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd | Enrolling by invitation ➔ Recruiting | Trial completion date: Mar 2025 ➔ Oct 2026 | Trial primary completion date: Jan 2025 ➔ Dec 2025

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

WX081-DDI: Drug-Drug Interaction and Food Effect of Sudapyridine(WX-081) With Itraconazole and Rifampin in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd

New P1 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Pharmacokinetic Study of Sudapyridine（WX-081）in Healthy Chinese Subjects (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd

New P1 trial

Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects. (PubMed, Clin Transl Sci) - "No QTc elongation was observed, and adverse events were not dose-dependent. Favorable exposure, tolerability, safety, and an extended MRT0-t suggest that WX-081 holds promise as a phase II development candidate for drug-resistant TB treatment."

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

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis. (PubMed, Antimicrob Agents Chemother) - "Here, we found synergistic activities between C and sudapyridine (S), a structural analog of bedaquiline (B)...Compared to the BPa(pretomanid)L regimen, SCT and SCTL demonstrated similar bactericidal and sterilizing activities...Our findings emphasize the efficacy and the potential clinical significance of combination therapy with ETC inhibitors. Additionally, cross-resistance exists not only between S and B but also between S/B and C. This is supported by our findings, as spontaneous S-resistant mutants exhibited mutations in Rv0678, which are associated with cross-resistance to B and C."

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

Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. (PubMed, mSphere) - "Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively."

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

WISH: Sudapyridine (WX-081) in RR/MDR/XDR-tuberculosis Patients (clinicaltrials.gov) - P3 | N=450 | Enrolling by invitation | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Jan 2025

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

Sudapyridine (WX-081) in Healthy Volunteers (clinicaltrials.gov) - P1 | N=82 | Completed | Sponsor: Shanghai Jiatan Pharmatech Co., Ltd

New P1 trial

Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus. (PubMed, Front Cell Infect Microbiol) - "Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of M. abscessus growth were assessed in vivo after fluorescently labelled bacilli and drugs were injected into zebrafish. When the concentration of WX-081 increased from 1.95µg/mL to 1/8 MTC(7.81µg/mL), the survival rate of zebrafish at 4-9 dpf decreased from 90.00% to 81.67%. WX-081 effectively inhibited M. abscessus growth in vitro and in vivo and prolonged survival of M. abscessus-infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for M. abscessus infection."

Journal • Infectious Disease