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RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection

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dc.contributor.author안상훈-
dc.date.accessioned2020-12-01T17:28:58Z-
dc.date.available2020-12-01T17:28:58Z-
dc.date.issued2020-07-
dc.identifier.issn0270-9139-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180293-
dc.description.abstractBackground 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.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherWiley-
dc.relation.isPartOfHEPATOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleRNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorMan-Fung Yuen-
dc.contributor.googleauthorIngolf Schiefke-
dc.contributor.googleauthorJung-Hwan Yoon-
dc.contributor.googleauthorSang Hoon Ahn-
dc.contributor.googleauthorJeong Heo-
dc.contributor.googleauthorJu Hyun Kim-
dc.contributor.googleauthorHenry Lik Yuen Chan-
dc.contributor.googleauthorKi Tae Yoon-
dc.contributor.googleauthorHartwig Klinker-
dc.contributor.googleauthorMichael Manns-
dc.contributor.googleauthorJoerg Petersen-
dc.contributor.googleauthorThomas Schluep-
dc.contributor.googleauthorJames Hamilton-
dc.contributor.googleauthorBruce D Given-
dc.contributor.googleauthorCarlo Ferrari-
dc.contributor.googleauthorChing-Lung Lai-
dc.contributor.googleauthorStephen A Locarnini-
dc.contributor.googleauthorRobert G Gish-
dc.identifier.doi10.1002/hep.31008-
dc.contributor.localIdA02226-
dc.relation.journalcodeJ00985-
dc.identifier.eissn1527-3350-
dc.identifier.pmid31654573-
dc.contributor.alternativeNameAhn, Sang Hoon-
dc.contributor.affiliatedAuthor안상훈-
dc.citation.volume72-
dc.citation.number1-
dc.citation.startPage19-
dc.citation.endPage31-
dc.identifier.bibliographicCitationHEPATOLOGY, Vol.72(1) : 19-31, 2020-07-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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