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Conference Paper: Short term RNA interference therapy in chronic hepatitis B using JNJ-3989 brings majority of patients to HBsAg < 100 IU/ml threshold

TitleShort term RNA interference therapy in chronic hepatitis B using JNJ-3989 brings majority of patients to HBsAg < 100 IU/ml threshold
Authors
Issue Date2019
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The International Liver Congress 2019, Vienna, Austria, 10-14 April 2019. Abstracts Book in Journal of Hepatology, 2019, v. 70 n. 1, Suppl., p. e51-e52, abstract no. PS-080 How to Cite?
AbstractBackground and aims: RNAi with JNJ-3989 (previously ARO-HBV) has shown promising reductions in circulating CHB viral parameters based on its design to silence mRNA from cccDNA and integrated sources (AASLD 2018). The ongoing phase 2 portion of AROHBV1001 assesses 3 doses of JNJ-3989 administered weekly to monthly in HBeAg pos (e pos) or neg (e neg) CHB patients. Herein we report reductions in HBsAg levels below important literature proposed thresholds and exploration of loading dose effect. Method: CHB patients (n = 56) received 3 subcutaneous doses of JNJ-3989. CHB cohorts 2b-5b (n = 4, e pos or neg, NUC treated or not) received monthly doses of 100, 200, 300 or 400 mg. Cohorts of e pos, NUC naïve and experienced CHB (cohorts 8, 9 respectively, n = 4 each) received 300 mg monthly. Loading dose cohorts (all n = 4, e pos or e neg, NUC treated or not) received bi-weekly or weekly doses of 100 mg (cohorts 6 and 7) or weekly doses of 200 mg (cohort 10) or 300 mg (cohort 11). Baseline NUC untreated CHB in any cohort receive NUCs from day1, continuing after JNJ-3989 dosing ends. HBsAg results reported are through day 113, 56 days after 3rd monthly dose when available or most recent in patients with data at least 14 days data following 3rd dose. In total, current HBsAg data is reported for 40 patients and safety for 56. Further data will be available at time of presentation. Results: No serious AEs or dropouts have been reported. Injection site AEs (all mild) occurred in ~12% of 171 injections. Mean max log10 declines in HBsAg were: 100 mg 1.9, 200 mg 1.7, 300 mg 1.7 and 400 mg 2.0 logs in cohorts 2b-5b and 2.3 in cohort 8, 2.5 in cohort 9. Giving JNJ-3989 more frequently (cohorts 6, 7, 10, 11) did not increase rate or extent of HBsAg knockdown; duration persisted at least 6 weeks after last dose. 97% (34 of 35) of patients reaching day 85 after first dose have > 1.0 log HBsAg reduction. Of 40 patients with ≥ 14 days follow-up after 3rd dose 3 had HBsAg < 100 IU/ml at baseline while currently 32 have achieved HBsAg < 100, 14 ≤ 10, 5 ≤ 1. Other viral parameters (HBV DNA, RNA, HBcrAg, HBeAg) above LLOQ at baseline improved. Conclusion: Monthly RNAi reduced all measurable viral products, including HBsAg in e pos and e neg CHB. JNJ-3989 rapidly reduces HBsAg to thresholds associated with improved chances of HBsAg sero-clearance with characteristics desirable for a cornerstone therapy in finite regimens aimed at HBsAg clearance in CHB. JNJ-3989 has been safe and well tolerated.
DescriptionOral Presentation - no. PS-080
Persistent Identifierhttp://hdl.handle.net/10722/275322
ISSN
2017 Impact Factor: 15.04
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorYuen, RMF-
dc.contributor.authorLocarnini, S-
dc.contributor.authorLim, TH-
dc.contributor.authorStrasser, S-
dc.contributor.authorSievert, W-
dc.contributor.authorCheng, W-
dc.contributor.authorThompson, A-
dc.contributor.authorGiven, B-
dc.contributor.authorSchluep, T-
dc.contributor.authorHamilton, J-
dc.contributor.authorCloherty, G-
dc.contributor.authorWong, DKH-
dc.contributor.authorSchwabe, C-
dc.contributor.authorJackson, K-
dc.contributor.authorFerrari, C-
dc.contributor.authorLai, CL-
dc.contributor.authorGish, RG-
dc.contributor.authorGane, E-
dc.date.accessioned2019-09-10T02:40:13Z-
dc.date.available2019-09-10T02:40:13Z-
dc.date.issued2019-
dc.identifier.citationThe International Liver Congress 2019, Vienna, Austria, 10-14 April 2019. Abstracts Book in Journal of Hepatology, 2019, v. 70 n. 1, Suppl., p. e51-e52, abstract no. PS-080-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/275322-
dc.descriptionOral Presentation - no. PS-080-
dc.description.abstractBackground and aims: RNAi with JNJ-3989 (previously ARO-HBV) has shown promising reductions in circulating CHB viral parameters based on its design to silence mRNA from cccDNA and integrated sources (AASLD 2018). The ongoing phase 2 portion of AROHBV1001 assesses 3 doses of JNJ-3989 administered weekly to monthly in HBeAg pos (e pos) or neg (e neg) CHB patients. Herein we report reductions in HBsAg levels below important literature proposed thresholds and exploration of loading dose effect. Method: CHB patients (n = 56) received 3 subcutaneous doses of JNJ-3989. CHB cohorts 2b-5b (n = 4, e pos or neg, NUC treated or not) received monthly doses of 100, 200, 300 or 400 mg. Cohorts of e pos, NUC naïve and experienced CHB (cohorts 8, 9 respectively, n = 4 each) received 300 mg monthly. Loading dose cohorts (all n = 4, e pos or e neg, NUC treated or not) received bi-weekly or weekly doses of 100 mg (cohorts 6 and 7) or weekly doses of 200 mg (cohort 10) or 300 mg (cohort 11). Baseline NUC untreated CHB in any cohort receive NUCs from day1, continuing after JNJ-3989 dosing ends. HBsAg results reported are through day 113, 56 days after 3rd monthly dose when available or most recent in patients with data at least 14 days data following 3rd dose. In total, current HBsAg data is reported for 40 patients and safety for 56. Further data will be available at time of presentation. Results: No serious AEs or dropouts have been reported. Injection site AEs (all mild) occurred in ~12% of 171 injections. Mean max log10 declines in HBsAg were: 100 mg 1.9, 200 mg 1.7, 300 mg 1.7 and 400 mg 2.0 logs in cohorts 2b-5b and 2.3 in cohort 8, 2.5 in cohort 9. Giving JNJ-3989 more frequently (cohorts 6, 7, 10, 11) did not increase rate or extent of HBsAg knockdown; duration persisted at least 6 weeks after last dose. 97% (34 of 35) of patients reaching day 85 after first dose have > 1.0 log HBsAg reduction. Of 40 patients with ≥ 14 days follow-up after 3rd dose 3 had HBsAg < 100 IU/ml at baseline while currently 32 have achieved HBsAg < 100, 14 ≤ 10, 5 ≤ 1. Other viral parameters (HBV DNA, RNA, HBcrAg, HBeAg) above LLOQ at baseline improved. Conclusion: Monthly RNAi reduced all measurable viral products, including HBsAg in e pos and e neg CHB. JNJ-3989 rapidly reduces HBsAg to thresholds associated with improved chances of HBsAg sero-clearance with characteristics desirable for a cornerstone therapy in finite regimens aimed at HBsAg clearance in CHB. JNJ-3989 has been safe and well tolerated.-
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.ispartofInternational Liver Congress 2019-
dc.titleShort term RNA interference therapy in chronic hepatitis B using JNJ-3989 brings majority of patients to HBsAg < 100 IU/ml threshold-
dc.typeConference_Paper-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hkucc.hku.hk-
dc.identifier.authorityYuen, RMF=rp00479-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.doi10.1016/S0618-8278(19)30092-1-
dc.identifier.hkuros304550-
dc.identifier.volume70-
dc.identifier.issue1, Suppl.-
dc.identifier.spagee51-
dc.identifier.epagee52-
dc.publisher.placeNetherlands-

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