alpibectir (BVL-GSK098) / BioVersys, GSK - LARVOL DELTA

ENABLE: A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination with Ethionamide (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: TASK Applied Science | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

BETO: A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098 (clinicaltrials.gov) - P2 | N=106 | Completed | Sponsor: TASK Applied Science | Recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ Apr 2024 | Trial primary completion date: Oct 2023 ➔ Apr 2024

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

ENABLE: A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination with Ethionamide (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: TASK Applied Science

New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Alpibectir: Early Qualitative and Quantitative Metabolic Profiling from a First Time in Human Study by Combining 19F-NMR, 1H-NMR and HRMS Analyses. (PubMed, Drug Metab Dispos) - "Significance Statement This study demonstrates that composite NMR and MS datasets help provide more complete data rationalisation and a confident assessment of human metabolism, and thereby has permitted early risk assessment and progression of activities relating to qualification of these risks for alpibectir. By combining the sensitivity of UPLC-HRMS, the selectivity of 19F-NMR, and structure-rich nature of 1H-NMR, an alternative approach for the detection and quantification of the drug-related material compared to traditional human ADME profiling using radiolabelled drug can be considered."

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

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug. (PubMed, J Antimicrob Chemother) - P1 | "Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food."

Journal • P1 data

Minimal inhibitory concentration of ethionamide alone and in combination with alpibectir on drug-sensitive and drug-resistant clinical isolates of Mycobacterium tuberculosis (ECCMID 2024) - No abstract available

Clinical • Combination therapy • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Early Bactericidal Activity of the Alpibectir-Ethionamide (AlpE) Combination Against Tuberculosis (CROI 2024) - P2 | "AlpE was well tolerated, safe and showed bactericidal activity similar to isoniazid in participants with tuberculosis. AlpE can be added to the growing list of novel antituberculosis agents for drug-susceptible and drug-resistant TB. The study is ongoing with escalating doses of alpibectir and ethionamide to optimize the combination."

Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Optimizing the use of current antituberculosis drugs to overcome drug resistance in Mycobacterium tuberculosis. (PubMed, Infect Dis Now) - "This objective can be achieved through two primary approaches: 1) Provided that toxicity concerns are not a limiting factor, increased dosing is a viable avenue, as demonstrated by rifampicin, isoniazid, and fluoroquinolones, for which escalated dosing has been effective; and 2) Employing enhancers such as drug activator boosters (ethionamide), efflux pump inhibitors, or hydrolytic enzyme inhibitors (kanamycin) can elevate the concentration of antibiotics in bacterial cells. These strategies offer the potential to mitigate antibiotic obsolescence and complement the discovery of new antibiotics."

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

BETO: A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098 (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: TASK Applied Science | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetics of BVL-GSK098 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: BioVersys AG | Active, not recruiting ➔ Completed | Trial completion date: Jun 2022 ➔ Jan 2023

Trial completion • Trial completion date

BETO: A Phase 2 Trial to Evaluate the EBA, Safety and Tolerability of Eto Alone and in Combination With BVL-GSK098 (clinicaltrials.gov) - P2 | N=105 | Not yet recruiting | Sponsor: TASK Applied Science

Combination therapy • New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetics of BVL-GSK098 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: BioVersys AG | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2022 ➔ May 2022

Enrollment closed • Trial primary completion date

The sulfoxide metabolite of ethionamide has antibacterial activity against Mycobacterium tuberculosis and is boosted by clinical candidate BVL-GSK098 (ECCMID 2022) - No abstract available

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

Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetics of BVL-GSK098 in Healthy Volunteers (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: BioVersys AG; Trial completion date: Jun 2021 ➔ Jun 2022; Trial primary completion date: Jun 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date

[VIRTUAL] How to turn an old drug into a potent, rapidly bactericidal and safer drug: clinical candidate BVL-GSK098 overcomes resistance to and potentiate the activity of ethionamide by boosting ethionamide bioactivation in Mycobacterium tuberculosis (ECCMID 2021) - "BVL-GSK098 has the potential to improve the safety profile of Eto by lowering the daily Eto doses for better patient tolerability and compliance . In addition, bEto overcomes Eto and INH resistance, is as rapidly bactericidal as INH and thus could be a valid replacement of INH in specific TB regimens."

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

[VIRTUAL] Bactericidal activity of ethionamide alone and boosted by BVL-GSK098 in an acute murine model of tuberculosis (ECCMID 2021) - "BVL-GSK098 0.5 mg/kg achieves maximum boosting effect on the in vivo bactericidal activity of Eto against M . tuberculosis enabling fast bactericidal activity and a dose reduction that may improve tolerance."

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

[VIRTUAL] Therapeutic efficacy of ethionamide boosted with BVL-GSK098 in an acute murine model of tuberculosis (ECCMID 2021) - No abstract available

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