RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection
- Authors
- Yuen M.-F.; Schiefke I.; Yoon J.-H.; Ahn S.H.; Heo J.; Kim J.H.; Lik Yuen Chan H.; Yoon K.T.; Klinker H.; Manns M.; Petersen J.; Schluep T.; Hamilton J.; Given B.D.; Ferrari C.; Lai C.-L.; Locarnini S.A.; Gish R.G.
- Issue Date
- Jul-2020
- Publisher
- John Wiley and Sons Inc.
- Citation
- Hepatology, v.72, no.1, pp.19 - 31
- Journal Title
- Hepatology
- Volume
- 72
- Number
- 1
- Start Page
- 19
- End Page
- 31
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/71684
- DOI
- 10.1002/hep.31008
- ISSN
- 0270-9139
- Abstract
- Background and Aims: ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all RNA transcripts derived from covalently closed circular DNA, leading to a reduction in viral antigens and hepatitis B virus (HBV) DNA. Approach and Results: We aimed to evaluate the depth of hepatitis B surface antigen (HBsAg) decline in response to multiple doses of ARC-520 compared to placebo (PBO) in two randomized, multicenter studies in nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)–experienced patients with hepatitis B early antigen (HBeAg)–negative (E-neg) or HBeAg-positive (E-pos) disease. A total of 58 E-neg and 32 E-pos patients were enrolled and received four monthly doses of PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg ARC-520 (n = 17 E-neg, 10 E-pos), or 2 mg/kg ARC-520 (n = 21 E-neg, 11 E-pos) concomitantly with NUC. HBsAg change from baseline to 30 days after the last ARC-520 dose were compared to PBO. Both E-neg and E-pos high-dose groups significantly reduced HBsAg compared to PBO, with mean reductions of 0.38 and 0.54 log IU/mL, respectively. HBsAg reductions persisted for approximately 85 days and >85 days after the last dose in E-neg and E-pos patients, respectively. The low-dose groups did not reach statistical significance in either study. E-pos patients showed a dose-dependent reduction in HBeAg from baseline. Mean maximum reduction was 0.23 and 0.69 log Paul Ehrlich IUs/mL in the low-dose and high dose ARC-520 groups respectively. ARC-520 was well tolerated, with only two serious adverse events of pyrexia possibly related to study drug observed. Conclusions: ARC-520 was active in both E-neg and E-pos, NUC-experienced HBV patients; but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin. © 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/71684)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.