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

Document Type

Conference Proceeding

Publication Date


Publication Title

J Hepatol


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.



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