Cited 75 times in
RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection
DC Field | Value | Language |
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dc.contributor.author | 안상훈 | - |
dc.date.accessioned | 2020-12-01T17:28:58Z | - |
dc.date.available | 2020-12-01T17:28:58Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180293 | - |
dc.description.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. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Wiley | - |
dc.relation.isPartOf | HEPATOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Man-Fung Yuen | - |
dc.contributor.googleauthor | Ingolf Schiefke | - |
dc.contributor.googleauthor | Jung-Hwan Yoon | - |
dc.contributor.googleauthor | Sang Hoon Ahn | - |
dc.contributor.googleauthor | Jeong Heo | - |
dc.contributor.googleauthor | Ju Hyun Kim | - |
dc.contributor.googleauthor | Henry Lik Yuen Chan | - |
dc.contributor.googleauthor | Ki Tae Yoon | - |
dc.contributor.googleauthor | Hartwig Klinker | - |
dc.contributor.googleauthor | Michael Manns | - |
dc.contributor.googleauthor | Joerg Petersen | - |
dc.contributor.googleauthor | Thomas Schluep | - |
dc.contributor.googleauthor | James Hamilton | - |
dc.contributor.googleauthor | Bruce D Given | - |
dc.contributor.googleauthor | Carlo Ferrari | - |
dc.contributor.googleauthor | Ching-Lung Lai | - |
dc.contributor.googleauthor | Stephen A Locarnini | - |
dc.contributor.googleauthor | Robert G Gish | - |
dc.identifier.doi | 10.1002/hep.31008 | - |
dc.contributor.localId | A02226 | - |
dc.relation.journalcode | J00985 | - |
dc.identifier.eissn | 1527-3350 | - |
dc.identifier.pmid | 31654573 | - |
dc.contributor.alternativeName | Ahn, Sang Hoon | - |
dc.contributor.affiliatedAuthor | 안상훈 | - |
dc.citation.volume | 72 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 19 | - |
dc.citation.endPage | 31 | - |
dc.identifier.bibliographicCitation | HEPATOLOGY, Vol.72(1) : 19-31, 2020-07 | - |
dc.identifier.rimsid | 67451 | - |
dc.type.rims | ART | - |
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