Imdusiran (AB-729) administered every 8 weeks in combination with 24 weeks of pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection leads to HBsAg loss in some subjects at end of IFN treatment
Recommended Citation
Yuen M, Heo J, Nahass RG, Lai-Hung Wong G, Burda T, Bhamidimarri KR, Hu T, Nguyen TT, Lim Y, Chen C, Gordon SC, Holmes J, Chuang W, Kohli A, Alkhouri N, Gray K, Thi EP, Medvedeva E, Eley T, Ganchua SC, Iott C, Eill E, Espiritu CL, Anderson M, Fortney T, Cloherty G, Sims KD. Imdusiran (AB-729) administered every 8 weeks in combination with 24 weeks of pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection leads to HBsAg loss in some subjects at end of IFN treatment. J Hepatol 2024; 80:S809-S810.
Document Type
Conference Proceeding
Publication Date
6-1-2024
Publication Title
J Hepatol
Abstract
Background and aims: Functional cure of CHB will require suppression of viral replication, reduction of HBsAg and use of an immunomodulator such as pegylated interferon alfa-2a (IFN) to enhance HBV-specific immunity. Imdusiran (AB-729) is a GalNAcconjugated single trigger siRNA that targets all HBV RNA transcripts and reduces all viral antigens including HBsAg. AB-729-201 is an ongoing Phase 2a study assessing 24 weeks of imdusiran followed by 12 or 24 weeks of IFN ± additional imdusiran doses in HBeAgnegative CHB subjects virally suppressed on nucleos (t)ide analogue (NA) therapy. Interim data through the end of the IFN treatment period (EOT) is available for all subjects. Method: Forty-three subjects received imdusiran 60 mg every 8 weeks (wks) for 24 wks (4 doses) during the lead-in phase. After Wk 24, subjects were randomized to 1 of 4 sub-groups: A1 (24 wks IFN + 2 imdusiran doses + NA; N = 12), A2 (24 wks IFN + NA; N = 13), B1 (12 wks IFN + 1 imdusiran dose + NA; N = 8) or B2 (12 wks IFN + NA; N = 10). After completing IFN ± imdusiran treatment, subjects continued NA therapy for 24 wks and stopped NA therapy if ALT <2 × upper limit of normal, HBV DNA undetectable and HBsAg <100 IU ml. Safety, antiviral and immunologic assessments were obtained. HBsAg was assessed via Roche Cobas Elecsys HBsAg II assay (lower limit of quantitation [LLOQ] = 0.05 IU ml) and results 10 IU L, and 5 7 had levels >100 IU L. In groups B1 B2, 0 18 subjects had HBsAg ≤LLOQ at EOT (Wk 40), although 2 reached 20, 000 IU ml with normal ALT levels. Conclusion: HBsAg ≤LLOQ with detectable anti-HBs was observed at EOT in 28% of subjects who received 4 or 6 doses of imdusiran plus 24 weeks of IFN, but in 0 subjects who received 4 or 5 doses of imdusiran plus 12 weeks of IFN. The study remains ongoing and additional EOT data, durability of EOT HBsAg loss, and preliminary immunology data for a subset of study subjects will be presented.
Volume
80
First Page
S809
Last Page
S810
