Professor Tarik Asselah presented an international study at the AASLD (American Association for Liver Disease) congress in Washington, D.C., demonstrating significant antiviral efficacy and favorable tolerability of the combination of Tobevibart (a monoclonal antibody) and Elebsiran (an antisense antibody against the hepatitis B virus) for the treatment of hepatitis delta. This study is published in the NEJM.
Abstract
Background: Both tobevibart (a monoclonal antibody) and elebsiran (a small interfering RNA) target hepatitis B virus surface antigen (HBsAg). Their efficacy and safety in the treatment of chronic hepatitis D virus (HDV) infection are unknown.
Methods: In this ongoing, phase 2, open-label trial, we randomly assigned participants to receive tobevibart plus elebsiran every 4 weeks or tobevibart monotherapy every 2 weeks. The primary end point was a combined response, defined by an HDV RNA level below the limit of detection or a decrease in the HDV RNA level of at least 2 log10 IU per milliliter from baseline (virologic response) and normalization of the alanine aminotransferase (ALT) level, at week 24.
Results: At week 24, a combined response was observed in 47% of participants (15 of 32) who received tobevibart plus elebsiran and in 70% of participants (23 of 33) who received tobevibart, with a virologic response in 100% (32 of 32) and 82% (27 of 33), respectively, and normalization of the ALT level in 47% (15 of 32) and 76% (25 of 33). At week 48, a combined response was observed in 56% of participants (18 of 32) with tobevibart plus elebsiran and 61% of participants (20 of 33) with tobevibart; undetectable HDV RNA (also known as target not detected, or TND; no amplification during reverse-transcriptase-polymerase-chain-reaction assay) in 66% (21 of 32) and 48% (16 of 33), respectively; normalization of the ALT level in 56% (18 of 32) and 61% (20 of 33); and an HBsAg level below 10 IU per milliliter in 91% (29 of 32) and 21% (7 of 33). No ALT flares were observed in participants starting tobevibart and elebsiran simultaneously or receiving tobevibart monotherapy. Through week 48, a total of 81% of participants who received tobevibart plus elebsiran and 94% of those who received tobevibart had at least one adverse event, primarily influenza-like illness and chills.
Conclusions: In this phase 2 trial, tobevibart plus elebsiran as well as tobevibart monotherapy decreased HDV RNA and ALT levels through week 48. Treatment with tobevibart plus elebsiran was associated with a high incidence of undetectable HDV RNA and of a decrease in the HBsAg level. (Funded by Vir Biotechnology; ClinicalTrials.gov number, NCT05461170.).