RG6084 / Roche - LARVOL DELTA

Efficacy and safety of xalnesiran in combination with the checkpoint inhibitor PD-L1 LNA in virologically suppressed participants with chronic hepatitis B: results from the Piranga phase 2, randomized, controlled, adaptive, open-label platform study (APASL 2025) - P2 | "Here, we report the primary and selected secondary and exploratory endpoint results of xalnesiran (RO7445482), a GalNAc-conjugated small interfering ribonucleic acid (siRNA) targeting HBsAg transcripts, in combination with PD-L1 LNA (RO7191863), a GalNAc-conjugated locked nucleic acid inhibiting the expression of the programmed death-ligand 1. The combination of xalnesiran with the checkpoint inhibitor PD-L1 LNA, either concurrently or sequentially, achieved limited efficacy on HBsAg loss and its durability. Xalnesiran with PD-L1 LNA was generally safe and well-tolerated. Table and Figure:Figure 1."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • P2 data • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Oncology

PHARMACOKINETIC/ PHARMACODYNAMIC MODELLING OF RG6084 EFFECTS ON HEPATITIS B SURFACE ANTIGEN AND ALANINE TRANSAMINASE TO INFORM PHASE 2 DOSING REGIMEN SELECTION (AASLD 2024) - "The developed PK and PK/PD model identifies separate exposure-response curves for ALT and HBsAg, and predicts the proportion of subjects that will exceed a defined ALT and HBsAg threshold. The model was successfully utilised in RG6084 Phase 2 dosing regimen selection[1] [2], whereby the chosen regimen is anticipated to meaningfully reduce the ALT liability without overtly impacting the HBsAg response."

P2 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1

Piranga: A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=281 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Jul 2024 | Trial primary completion date: Oct 2024 ➔ Jul 2024

Combination therapy • Trial completion • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Piranga: A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2025 ➔ Jul 2025

Combination therapy • Trial completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=275 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2023 ➔ Nov 2024 | Trial primary completion date: Mar 2023 ➔ May 2024

Combination therapy • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1