Abstract

Background:

This open-label study assessed the safety and efficacy of vebicorvir (VBR)+AB-729+nucleos(t)ide reverse transcriptase inhibitor (NrtI) in virologically suppressed (VS) patients (pts) with hepatitis B e antigen (eAg) negative chronic hepatitis B infection (NCT04820686). VBR is a 1st-generation core inhibitor and AB-729 is a single trigger GalNAc-siRNA targeting all HBV RNA transcripts. Initial end of treatment (EOT) responses were previously described. Here, we report additional EOT data and preliminary off-treatment responses.

Methods:

Sixty-five VS eAg negative pts were randomized to receive VBR+AB-729+NrtI (n=32), VBR+NrtI (n=16), or AB-729+NrtI (n=17) for 48 weeks (wks). VBR 300 mg was given orally once daily and AB-729 as a 60 mg subcutaneous injection every 8 wks. Based on Wk 48 lab results, pts with ALT <2x upper limit of normal + HBV DNA <lower limit of quantification (LLOQ) + hepatitis B surface antigen (sAg) <100 IU/mL could discontinue all treatment and enter follow-up. Patients not meeting this criterion continued NrtI alone during follow-up. Virologic markers included sAg (Abbott Architect; LLOQ=0.05 IU/mL) and HBV DNA (Cobas TaqMan; LLOQ=20 IU/mL). Safety was assessed by adverse events (AEs) and lab parameters.

Results:

Baseline characteristics were similar across treatments. Treatments were well tolerated with 9% (3/32), 6% (1/16), and 6% (1/17) of pts discontinuing treatment due to an AE in the VBR+AB-729+NrtI, VBR+NrtI, and AB-729+NrtI arms, respectively. AEs on treatment were generally Grade 1/2 and reported in 81% (26/32), 75% (12/16), and 71% (12/17) of pts in the VBR+AB-729+NrtI, VBR+NrtI, and AB-729+NrtI arms, respectively. There was a single serious AE (COVID-19 pneumonia in a VBR+AB-729+NrtI recipient). At time of analysis, while no pts had HBsAg seroconversion, 16/26, 0/15, and 8/10 pts with available Wk 48 data met criteria to stop all treatment in the VBR+AB-729+NrtI, VBR+NrtI, and AB-729+NrtI arms, respectively. Of these, 12 pts who received VBR+AB-729+NrtI and 7 who received AB-729+NrtI discontinued all treatment. 8 wks after discontinuing all treatment, continued suppression of sAg <100 IU/mL was observed in 89% (8/9) and 83% (5/6) of pts with available data receiving VBR+AB-729+NrtI and AB-729+NrtI, respectively (Table).

Conclusion:

Treatments were well tolerated. Available data indicate that adding VBR to AB-729+NrtI does not result in significantly greater on- or post-treatment improvements in markers of active HBV infection vs AB-729+NrtI.