GSK4532990 / GSK, Arrowhead - LARVOL DELTA

SKYLINE: Dose Exploration Study of GSK4532990 in. Participants With NASH or Suspected NASH (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

STARLIGHT: A Study to Investigate the Safety and Efficacy of GSK4532990 Compared With Placebo in Adult Participants Aged 18 to 65 Years With Alcohol-related Liver Disease (clinicaltrials.gov) - P2 | N=393 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2027 ➔ Aug 2027

Enrollment open • Trial completion date • Hepatology

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2 | N=284 | Active, not recruiting | Sponsor: GlaxoSmithKline | Trial completion date: May 2026 ➔ Apr 2027

Trial completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

A quantitative systems pharmacology model identifies mechanisms attenuated by knockdown of HSD17B13 expression and associated with a reduction in hepatocellular ballooning (EASL 2025) - P1/2 | "ARO-HSD, a hepatocyte-targeted siRNA therapeutic designed to silence HSD17B13 expression, improved markers of liver injury in participants with MASH in a Phase 1/2a clinical trial (NCT04202354)... This QSP study suggests that TG lipolysis and mitochondrial biogenesis may be a key MoA behind HSD17B13 knockdown. The QSP model predicts that HSD17B13 knockdown results in reductions in ALT, as seen in the Phase 1/2a trial, and additionally reduces PRO-C3. The small dataset available for calibration limits the strength of the conclusions that can be drawn."

Hepatology • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2 | N=271 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2025 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

STARLIGHT: A Study to Investigate the Safety and Efficacy of GSK4532990 Compared With Placebo in Adult Participants Aged 18 to 65 Years With Alcohol-related Liver Disease (clinicaltrials.gov) - P2 | N=393 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Hepatology

A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of VSA006 in Chinese NASH Patients (clinicaltrials.gov) - P2 | N=45 | Not yet recruiting | Sponsor: Visirna Therapeutics HK Limited

New P2 trial • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

SKYLINE: Dose Exploration Study of GSK4532990 in Participants With NASH or Suspected NASH (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

SKYLINE: Dose Exploration Study of GSK4532990 in Participants With NASH or Suspected NASH (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: GlaxoSmithKline | Phase classification: P2a ➔ P2

Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2 | N=246 | Recruiting | Sponsor: GlaxoSmithKline | Phase classification: P2b ➔ P2

Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

SKYLINE: Dose Exploration Study of GSK4532990 in Participants With NASH or Suspected NASH (clinicaltrials.gov) - P2a | N=48 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2a trial • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2b | N=246 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • TIMP1

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2b | N=246 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • TIMP1

A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis. (PubMed, J Hepatol) - P1/2 | "ARO-HSD was well tolerated at doses ≤200 mg. This proof-of-concept study demonstrated that short-term treatment with ARO-HSD reduces hepatic HSD17β13 mRNA and protein, which is accompanied by reductions in ALT. Impacts and Implications: TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT04202354."

Journal • P1/2 data • Hepatology • Non-alcoholic Steatohepatitis

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2b | N=246 | Not yet recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • TIMP1

HORIZON: Phase 2b Study of GSK4532990 in Adults With NASH (clinicaltrials.gov) - P2b | N=246 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2b trial • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • TIMP1