Multiple-dose ARC-520 therapy may result in significant and continued reductions in viral antigens and hepatitis B virus (HBV) ribonucleic acid (RNA) in patients with chronic HBV, according to study results published in Gut. Results also suggested that hepatitis B surface antigen (HBsAg) seroclearance was achievable and that long-term oral nucleotide or nucleoside analogue therapy could be stopped once functional cure was achieved.
A team of international investigators conducted an extension phase 1b study (ClinicalTrials.gov Identifier: NCT02065336) to characterize serological, virological, and histological profiles during and after multidose ARC-520 treatment in patients with chronic HBV. The analysis consisted of an extension cohort of patients who had previously received a single dose of ARC-520.
In the current analysis, 8 patients of Chinese ethnicity (median age, 38.4 years; male-to-female ratio, 5:3) were treated with 4 to 9 doses of multidose ARC-520 4 times a week in combination with entecavir. Hepatic biopsies were taken from 6 patients, and intrahepatic and serum HBV deoxyribonucleic acid (DNA), HBV RNA, and viral antigens were measured.
Follow-up ranged from 28.9 to 30.4 months after the last multidose. Of the 3 patients who were positive for hepatitis B E antigen (HBeAg), all individuals had significant reductions in HBsAg, HBeAg, core-related antigen, and HBV RNA; 2 patients underwent HBeAg seroconversion. Additionally, 1 of the patients achieved HBsAg seroconversion, while the other 2 patients had significantly reduced HBsAg levels after more than 30 months posttreatment.
After more than 29 months, 4 of 5 HBeAg-negative patients had modest reductions in surface antigen levels, and 1 patient achieved HBsAg serconversion and was negative for liver HBsAg staining.
In addition, alanine aminotransferase flares were reported in 3 patients after HBsAg reductions, which was suggestive of immune activation.
“In conclusion, [multidose] ARC-520 was associated with sustained and profound reductions of HBsAg and other viral components, in some cases probably accompanied by host responses and further dynamic changes in viral parameters,” the investigators noted.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Yuen M-F, Wong D K-H, Schluep T, et al. Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment. Gut. Published online March 12, 2021. doi: 10.1136/gutjnl-2020-323445