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Conference Paper: RNA interference therapy with ARC-520 Injection results in long term off-therapy antigen reductions in treatment naïve, HBeAg positive and negative patients with chronic HBV

TitleRNA interference therapy with ARC-520 Injection results in long term off-therapy antigen reductions in treatment naïve, HBeAg positive and negative patients with chronic HBV
Authors
Issue Date2018
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The International Liver Congress 2018 (ILC 2018), Paris, France, 11–15 April 2018. Abstract Book in Journal of Hepatology, 2018, v. 68 n. Suppl. 1, p. S526 How to Cite?
AbstractBackground and Aims: ARC-520 Injection (ARC), a RNA interference drug, targets cccDNA-derived mRNA in chronic hepatitis B patients (CHB).We previously reported HBsAg reduction and safety in a multidose extension study. Here we report additional antigen reductions observed off-therapy during a 6-month follow-up period. Method: 8 CHB (5 HBeAg-neg, 3 HBeAg-pos) received up to 9 doses of 4 mg/kg ARC once every 4 weeks with daily entecavir (ETV). Treatment naïve CHB who previously received a single IV dose of 4 mg/kg ARC and started daily ETV on the same day were eligible. Viral DNA and antigen knockdown (KD) were measured at regular intervals [qHBsAg, HB core-related antigen (qHBcrAg) in all, qHBeAg in HBeAg-pos]. Patients continued their daily ETV post ARC and were followed for an additional 6 months. Results: Patients received ETV for 34 to 44weeks after a single dose of ARC before receiving the first ARC dose of the multi-dose extension. After a single dose of ARC, qHBsAg in 3 of 3 HBeAg-pos and 1 of 5 HBeAg-neg remained below baseline. Multi-dose re-challenge resulted in additional qHBsAg KD in all CHB. Two of three HBeAgpos and one of five HBeAg-neg had mild ALT elevations post ARC which coincided with additional antigen reductions. In the HBeAgpos, mean HBsAg reduction w as 3.0 log and max reduction 4.6log with one patient achieving an HBsAg level of 1 IU/ml. This patient seroconverted for HBeAg post ARC with mean HBeAg reduction of 2.8 log and max reduction of 4.2 log to LLOQ. Mean HBcrAg reductionwas 3.4 log with max reduction of 6.1log in HBeAg-pos. In HBeAg-neg, mean HBsAg KD was 1.0 log and maximum was 2.1 log, HBcrAg reduction was 0.7 log in the only patient positive for this marker. Conclusion: (1) Consistent with our previous reports, ARC was more active in HBeAg-pos, presumably due to more cccDNA-driven antigen production in treatment naïve HBeAg-pos and a higher fraction of qHBsAg from integrated DNA in HBeAg-neg. (2) Mild ALT elevations off ARC therapy coincided with additional antigen reductions in 2/3 HBeAg-pos and 1/5 HBeAg-neg. (3) Antigen reduction through RNAi in combination with oral ETV may lead to sustained control of CHB off-therapy.
DescriptionPoster Presentation - no. FRI-362
The Congress was hosted by The European Association for the Study of the Liver (EASL)
Persistent Identifierhttp://hdl.handle.net/10722/262444
ISSN
2017 Impact Factor: 15.04
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorYuen, RMF-
dc.contributor.authorLiu, SHK-
dc.contributor.authorGiven, B-
dc.contributor.authorSchluep, T-
dc.contributor.authorHamilton, J-
dc.contributor.authorLai, CL-
dc.contributor.authorLocarnini, S-
dc.contributor.authorJackson, K-
dc.contributor.authorLai, JY-
dc.contributor.authorFerrari, C-
dc.contributor.authorGish, RG.-
dc.date.accessioned2018-09-28T04:59:25Z-
dc.date.available2018-09-28T04:59:25Z-
dc.date.issued2018-
dc.identifier.citationThe International Liver Congress 2018 (ILC 2018), Paris, France, 11–15 April 2018. Abstract Book in Journal of Hepatology, 2018, v. 68 n. Suppl. 1, p. S526-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/262444-
dc.descriptionPoster Presentation - no. FRI-362-
dc.descriptionThe Congress was hosted by The European Association for the Study of the Liver (EASL)-
dc.description.abstractBackground and Aims: ARC-520 Injection (ARC), a RNA interference drug, targets cccDNA-derived mRNA in chronic hepatitis B patients (CHB).We previously reported HBsAg reduction and safety in a multidose extension study. Here we report additional antigen reductions observed off-therapy during a 6-month follow-up period. Method: 8 CHB (5 HBeAg-neg, 3 HBeAg-pos) received up to 9 doses of 4 mg/kg ARC once every 4 weeks with daily entecavir (ETV). Treatment naïve CHB who previously received a single IV dose of 4 mg/kg ARC and started daily ETV on the same day were eligible. Viral DNA and antigen knockdown (KD) were measured at regular intervals [qHBsAg, HB core-related antigen (qHBcrAg) in all, qHBeAg in HBeAg-pos]. Patients continued their daily ETV post ARC and were followed for an additional 6 months. Results: Patients received ETV for 34 to 44weeks after a single dose of ARC before receiving the first ARC dose of the multi-dose extension. After a single dose of ARC, qHBsAg in 3 of 3 HBeAg-pos and 1 of 5 HBeAg-neg remained below baseline. Multi-dose re-challenge resulted in additional qHBsAg KD in all CHB. Two of three HBeAgpos and one of five HBeAg-neg had mild ALT elevations post ARC which coincided with additional antigen reductions. In the HBeAgpos, mean HBsAg reduction w as 3.0 log and max reduction 4.6log with one patient achieving an HBsAg level of 1 IU/ml. This patient seroconverted for HBeAg post ARC with mean HBeAg reduction of 2.8 log and max reduction of 4.2 log to LLOQ. Mean HBcrAg reductionwas 3.4 log with max reduction of 6.1log in HBeAg-pos. In HBeAg-neg, mean HBsAg KD was 1.0 log and maximum was 2.1 log, HBcrAg reduction was 0.7 log in the only patient positive for this marker. Conclusion: (1) Consistent with our previous reports, ARC was more active in HBeAg-pos, presumably due to more cccDNA-driven antigen production in treatment naïve HBeAg-pos and a higher fraction of qHBsAg from integrated DNA in HBeAg-neg. (2) Mild ALT elevations off ARC therapy coincided with additional antigen reductions in 2/3 HBeAg-pos and 1/5 HBeAg-neg. (3) Antigen reduction through RNAi in combination with oral ETV may lead to sustained control of CHB off-therapy.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.relation.ispartofThe International Liver Congress 2018 (ILC 2018)-
dc.titleRNA interference therapy with ARC-520 Injection results in long term off-therapy antigen reductions in treatment naïve, HBeAg positive and negative patients with chronic HBV-
dc.typeConference_Paper-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.emailLiu, SHK: drkliu@hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hkucc.hku.hk-
dc.identifier.authorityYuen, RMF=rp00479-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.doi10.1016/S0168-8278(18)31302-3-
dc.identifier.hkuros292255-
dc.identifier.volume68-
dc.identifier.issueSuppl. 1-
dc.identifier.spageS526-
dc.identifier.epageS526-
dc.publisher.placeNetherlands-

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