Preliminary safety and antiviral activity of AB-729 combination treatment with pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection
Recommended Citation
Yuen M, Heo J, Nahass RG, Wong G, Burda T, Bhamidimarri KR, Hu T, Nguyen T, Lim Y, Chen C, Gordon SC, Holmes J, Chuang W, Kohli A, Alkhouri N, Gray K, Thi EP, Medvedeva E, Eley T, Sims K. Preliminary safety and antiviral activity of AB-729 combination treatment with pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection. J Hepatol 2023; 78:125.
Document Type
Conference Proceeding
Publication Date
6-1-2023
Publication Title
J Hepatol
Keywords
antivirus agent, endogenous compound, hepatitis B surface antigen, hepatitis B(e) antigen, peginterferon alpha2a, adult, antiviral activity, chronic hepatitis B, conference abstract, controlled study, data analysis, drug combination, drug safety, drug therapy, drug withdrawal, female, follow up, hepatitis B virus test kit, human, limit of quantitation, major clinical study, male, middle aged, neutropenia, randomized controlled trial
Abstract
Background and aims: AB-729is anN-Acetylgalactosamine(GalNAc)- conjugated single trigger RNA interference therapeutic that targets all HBVRNAtranscripts, resulting in suppression of viral replicationand all viral antigens. AB-729-201 is an ongoing Phase 2a study assessing 24 weeks of AB-729 followed by 12 or 24 weeks of pegylated interferon alfa-2a (IFN) with or without additional AB-729 doses in virally suppressed, HBeAg-negative CHB subjects. We report interim data through 12 weeks of IFN treatment for the first 12 subjects. Method: Forty-three CHB subjects, virally suppressed on stable nucleos (t)ide analog (NA) therapy, were all enrolled to receive AB- 729 60 mg every 8 weeks for 24 weeks (4 doses) during the lead-in phase. After Week 24, the subjects were randomized to 1 of 4 subgroups: A1 (24 weeks IFN + AB-729+NA), A2 (24 weeks IFN + NA), B1 (12 weeks IFN + AB-729 + NA) or B2 (12 weeks IFN + NA). After completing IFN ± AB-729 treatment, subjects continued NA therapy only for an additional 24 weeks and were then evaluated for NA discontinuation based on protocol criteria (ALT <2 x upper limit of normal, undetectable HBV DNA, confirmed HBsAg <100 IU/ml). Safety and antiviral assessments were obtained every 2-4 weeks. HBsAg quantification was assessed via Roche Cobas Elecsys HBsAg II quant II assay (lower limit of quantitation [LLOQ] = 0.05 IU/ml). Results: The median subject age was 46 years, 72% were male, and 79% were Asian. To date, 32 of 43 subjects have been randomized to the 4 IFN sub-groups after completing the 24-week AB-729 lead-in period. The mean (standard error [SE]) baseline HBsAg level for all 43 subjects was 2.98 (0.07) log10 IU/ml and the median (range) was 2.92 (2.7-3.4) log10 IU/ml. The mean (SE) HBsAg decline observed atWeek 24 was -1.65 log10 (0.10, n = 34). All subjects had HBsAg declines of approximately 1 log10 or more from baseline, and 28 of the 32 (88%) randomized subjects reached HBsAg <100 IU/ml. After 6weeks of IFN treatment, mean HBsAg declines from baseline ranged from -1.53 to -2.49 log10 across the 4 sub-groups (3-5 subjects/group), and after 12 weeks of IFN, mean HBsAg declines ranged from -0.74 to -2.20 log10 (2-4 subjects/group). Three subjects had intermittent HBsAg 1.6 log10 after 24 weeks of treatment, comparable to other AB-729 studies. HBsAg levels <100 IU/ml were noted in 88% of the subjects. This interim data analysis suggests addition of IFNwaswell tolerated, and AB-729 + IFN appears to result in continued HBsAg declines in most subjects with 2 subjects reaching HBsAg
PubMed ID
Not assigned.
Volume
78
First Page
125
