Delving into the Latest Updates on ARC-520 with Synapse

Overview

Basic Info

Drug Type

siRNA

Synonyms

Target-

Mechanism

RNA interference

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Hepatitis B, ChronicHepatitis D

Originator Organization

Arrowhead Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Arrowhead Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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ObjectiveWe examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.DesignThe present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4–9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.ResultsAll patients had 28.9–30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of −1.7 and −3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.ConclusionsMD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.Trial registration numberNCT02065336.

01 Jul 2020·HepatologyQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: Heo, Jeong ; Schiefke, Ingolf ; Given, Bruce D. ; Gish, Robert G. ; Manns, Michael ; Klinker, Hartwig ; Ferrari, Carlo ; Kim, Ju Hyun ; Ahn, Sang Hoon ; Yoon, Ki Tae ; Schluep, Thomas ; Yoon, Jung‐Hwan ; Yuen, Man‐Fung ; Petersen, Joerg ; Hamilton, James ; Locarnini, Stephen A. ; Lik Yuen Chan, Henry ; Lai, Ching‐Lung

Background and AimsARC‐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 ResultsWe 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.ConclusionsARC‐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.

01 Apr 2018·Nature Reviews Gastroenterology & HepatologyQ1 · MEDICINE

No cure for hepatitis B and D without targeting integrated viral DNA?

Q1 · MEDICINE

Article

Author: Cornberg, Markus ; Manns, Michael P

RNA interference (RNAi) is a novel concept to target transcripts derived from HBV covalently closed circular DNA. The study by Wooddell et al. investigates the RNAi-based therapy ARC-520 in patients and chimpanzees with chronic HBV infection and uncovers HBV DNA integration as a crucial source of hepatitis B surface antigen, which has not been considered in current strategies to accomplish HBV cure.

1

News (Medical) associated with ARC-520

10 Dec 2013

·www.biospace.com

Arrowhead Research Corporation Presents Phase 1 Data On ARC-520 At HepDART 2013

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that COO and Head of R&D, Bruce Given, M.D., presented data on the Phase 1 clinical study of ARC-520, the company’s clinical candidate for the treatment of chronic hepatitis B infection, at the HepDART 2013 conference being held on The Big Island, Hawaii. Help employers find you! Check out all the jobs and post your resume.

100 Deals associated with ARC-520

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis D	Phase 2	NZ	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	AU	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	KR	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	MD	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	BG	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	TH	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	TW	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis D	Phase 2	CN	Arrowhead Pharmaceuticals, Inc.	01 Dec 2015
Hepatitis B, Chronic	Phase 2	HK	Arrowhead Pharmaceuticals, Inc.	01 Mar 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02604212 (CTgov)	Phase 2	Hepatitis B, Chronic	32	antihistamine+tenofovir+ARC-520+Entecavir (ARC-520 1.0 mg/kg)	gldpuyhplo(chghvrewlx) = grufkklwkw lppumytqky (emxbhkyhzy, xyoaeicvik - qfaqhdjnjg) View more	-	16 Apr 2019
				antihistamine+tenofovir+ARC-520+Entecavir (ARC-520 2.0 mg/kg)	gldpuyhplo(chghvrewlx) = kwlfzkffgi lppumytqky (emxbhkyhzy, kzciyudmos - thxilaliba) View more
NCT02738008 (CTgov)	Phase 2	Hepatitis B, Chronic	12	ARC-520 (Heparc-2002: ARC-520 1.0 mg/kg)	(fqfmhcpxqa) = zuutcsbdcc jghhbwhdkv (hqrqgibfmp, mxvdcyfgdq - yfyylnliin) View more	-	16 Apr 2019
				ARC-520 (Heparc-2002: ARC-520 2.0 mg/kg)	(fqfmhcpxqa) = uawlixgilc jghhbwhdkv (hqrqgibfmp, uqotxuiner - ngmzwqdafm) View more
NCT02604199 (CTgov)	Phase 2	Hepatitis B, Chronic	58	antihistamine+tenofovir+ARC-520 Injection+Entecavir (ARC-520 Injection 1 mg/kg)	zksmiiczsi(evcysxrxfh) = cgxvguyjyc ancnapowhn (egkdusfsrd, irvdnpwqrt - gpkuomovps) View more	-	16 Apr 2019
				antihistamine+tenofovir+ARC-520 Injection+Entecavir (ARC-520 Injection 2 mg/kg)	zksmiiczsi(evcysxrxfh) = dvqvqyapqz ancnapowhn (egkdusfsrd, gbcevqfdlo - aykfhxfsor) View more
NCT02577029 (MONARCH, CTgov)	Phase 2	Hepatitis B, Chronic \| Hepatitis D	79	antihistamine+ARC-520 (Cohort 1)	znbqxcavso(zqvyuhkhcu) = lholmmsyii guexnjlztx (wpitkiuxbg, iitaybclkf - lmqikhtvlq) View more	-	12 Apr 2019
				antihistamine+tenofovir disoproxil+ARC-520+pegylated interferon alpha 2a+entecavir (Cohort 2)	znbqxcavso(zqvyuhkhcu) = lbaxsazobh guexnjlztx (wpitkiuxbg, czhwoaceta - yuuusivgxa) View more
NCT02535416 (CTgov)	Phase 1	-	40	cetirizine+ARC-520 (ARC-520 Cohort 1)	dktniofdqf(zbxuxzhrys) = drdgkjaoww dmhnslxmly (bvawaibsku, qzjlvudxvr - idaonvmqkm) View more	-	26 Feb 2018
				cetirizine+ARC-520 (ARC-520 Cohort 2A)	dktniofdqf(zbxuxzhrys) = zbtcxgxahz dmhnslxmly (bvawaibsku, bzubijznjp - jrpiyttbxw) View more
NCT02452528 (CTgov)	Phase 2	Hepatitis B, Chronic	4	tenofovir+ARC-520+Entecavir+diphenhydramine (ARC-520)	(iwnvytxwoi) = horwoezcfo escmhgoauc (toliywmqpg, ghzufkukxb - bmolnlldya) View more	-	01 Nov 2017
				Placebo+tenofovir+Entecavir+diphenhydramine (Placebo)	(iwnvytxwoi) = cnzsvopjll escmhgoauc (toliywmqpg, humwaxvfhn - vsvbveknhb) View more