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

• DOI: 10.1002/hep.31008
• Publication Date: 2019-10-26T15:09:43Z
• Authors: Man‐Fung Yuen; Ingolf Schiefke; Jung‐Hwan Yoon; Sang Hoon Ahn; Jeong Heo; Ju Hyun Kim; Henry Lik Yuen Chan; Ki Tae Yoon; Hartwig Klinker; Michael Manns; Joerg Petersen; Thomas Schluep; James Hamilton; Bruce D. Given; Carlo Ferrari; Ching‐Lung Lai; Stephen A. Locarnini; Robert G. Gish
• Keywords: Hepatitis B

ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all transcripts derived from covalently closed circular DNA, leading a reduction in viral antigens and hepatitis B virus (HBV) DNA.We aimed evaluate depth of surface antigen (HBsAg) decline response multiple doses ARC-520 compared placebo (PBO) two randomized, multicenter studies nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)-experienced patients with early (HBeAg)-negative (E-neg) or HBeAg-positive (E-pos) disease. A total 58 E-neg 32 E-pos were enrolled received four monthly PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg 17 10 2 21 E-pos) concomitantly NUC. HBsAg change baseline 30 days after last dose PBO. Both high-dose groups significantly reduced PBO, mean reductions 0.38 0.54 log IU/mL, respectively. persisted for approximately 85 >85 patients, The low-dose did not reach statistical significance either study. showed dose-dependent HBeAg baseline. Mean maximum 0.23 0.69 Paul Ehrlich IUs/mL high well tolerated, only serious adverse events pyrexia possibly related study drug observed.ARC-520 active both E-pos, NUC-experienced HBV patients; but absolute moderate, due expression integrated indicating need RNAi therapeutics that can target regardless origin.