Bepirovirsen for Chronic HBV Functional Cure: FDA Criteria and B-Well Data

　　1.Approval Snapshot

　　Bepirovirsen sodium(Hibsago)is an antisense oligonucleotide injected subcutaneously.

　　FDA approval 20 Oct 2026:with nucleos(t)ide analogue​for adults with chronic HBV who are:

　　non-cirrhotic;

　　on NrtI≥6 months;

　　HBV DNA suppressed;

　　HBsAg≤3000 IU/mL by authorized assay.

　　Not for cirrhosis,viremic patients,HBsAg>3000 IU/mL,monotherapy replacement,or pediatric use.

　　2.Why“Functional Cure”

　　NA therapy suppresses replication but HBsAg often persists.

　　Functional cure=after stopping all HBV therapy:

　　HBsAg undetectable;

　　HBV DNA below sensitive limit;

　　not cccDNA eradication.

　　Bepirovirsen aims to lower antigen burden so selected patients may discontinue NA under protocol.

　　3.Mechanism

　　ASO binds HBV RNA,promotes degradation:

　　less pgRNA/mRNA;

　　lower HBsAg and viral protein;

　　possible immune re-engagement;

　　no direct cytotoxic kill,no cccDNA clearance.

　　4.B-Well 1/2 Data

　　Global randomized placebo-controlled,weekly SC~24 weeks,follow-up to week 72.

　　Pooled:

　　HBsAg≤3000 IU/mL:19%​functional cure(233/1220)vs 0 placebo;

　　HBsAg≤1000 IU/mL:26%​vs 0;

　　HBsAg≤100 IU/mL by week 72:~49%;

　　Chinese subgroup consistent but subgroup-level only.

　　Limits:~80%not cured;NA stop not guaranteed;baseline HBsAg drives benefit.

　　5.Dosing

　　subcutaneous weekly,up to~24 weeks;

　　continue baseline NrtI;

　　continue antiviral≥24 weeks after last dose;

　　stop only if criteria met per prescriber;

　　no self-stop of nucleos(t)ide.