{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:35:15Z","timestamp":1768419315069,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bepirovirsen is an antisense oligonucleotide currently in Phase 3 development to treat chronic hepatitis B virus (HBV) infection. Given the importance of coadministration of bepirovirsen and standard\u2010of\u2010care nucleos(t)ide analogs (NAs), we evaluated drug\u2013drug interactions (DDIs) between bepirovirsen, entecavir (ETV), and tenofovir (TFV) using in vitro and clinical data obtained through innovative study design and sampling strategy. Static models employing in vitro data indicated that bepirovirsen is not a direct inhibitor or inducer of most drug\u2010metabolizing enzymes or an inhibitor or substrate of drug transporters and poses no clinical DDI risk against NAs. Bepirovirsen plasma pharmacokinetic parameters and concentration\u2013time profiles in patients with chronic HBV in the CS3 study (NCT02981602) were similar with or without ETV or TFV coadministration, indicating no effect of NA coadministration on bepirovirsen pharmacokinetics. In patients with chronic HBV receiving both bepirovirsen and ETV or TFV in the B\u2010Clear study (NCT04449029), NA plasma concentrations and pharmacokinetic parameters were similar to those published without bepirovirsen coadministration, suggesting no effect of bepirovirsen coadministration on NA pharmacokinetics. This analysis demonstrated no DDI potential between bepirovirsen and NAs, suggesting that dedicated clinical DDI studies are not required. Bepirovirsen is currently being evaluated in Phase 3 studies in combination with NA.<\/jats:p>","DOI":"10.1002\/cpdd.1518","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T12:38:36Z","timestamp":1739536716000},"page":"281-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lack of Pharmacokinetic Drug\u2013Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs"],"prefix":"10.1002","volume":"14","author":[{"given":"Kelong","family":"Han","sequence":"first","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir S.","family":"Youssef","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mindy","family":"Magee","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Hood","sequence":"additional","affiliation":[{"name":"GSK, DMPK \u2010 Disposition &amp; Biotransformation  Stevenage Hertfordshire UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Tracey","sequence":"additional","affiliation":[{"name":"GSK, PBPK Modelling, DMPK, Preclinical Sciences, Research Technologies, R&amp;D  Stevenage Hertfordshire UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Kwoh","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc.  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[{"name":"GSK, Clinical Research, Hepatology  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Paff","sequence":"additional","affiliation":[{"name":"GSK, Development Medicine  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Nader","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00197-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14020434"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224773"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr388"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000431"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1436"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-021-01589-x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ygh2.393"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15522"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2023.2277389"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210027"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.08.020"},{"key":"e_1_2_10_15_1","unstructured":"YouS SinghJ SmithS et\u00a0al.Treatment with GSK3228836 leads to HBsAg reduction and induction of interferon gamma related proteins and chemokines in a Phase 2a randomized double\u2010blind placebo\u2010controlled study (Poster No. PO\u20102173).European Association for the Study of the Liver.2021.https:\/\/www.postersessiononline.eu\/173580348_eu\/congresos\/ILC2021\/aula\/\u2010PO_2173_ILC2021.pdf."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01513-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","unstructured":"YouS DelahayeJ ErmlerM et\u00a0al.Bepirovirsen antisense oligonucleotide (ASO) against hepatitis B virus (HBV) harbors intrinsic immunostimulatory activity via toll\u2010like receptor 8 (TLR8) preclinically correlating with clinical efficacy from the Phase 2a study. European Association for the Study of the Liver (Poster No. SAT439).2022.https:\/\/www.postersessiononline.eu\/173580348_eu\/congresos\/ILC2022\/aula\/\u2010SAT_439_ILC2022.pdf.","DOI":"10.1016\/S0168-8278(22)02041-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2022.0054"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645080-00003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000101"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0779"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/0003088-200948010-00003"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2015.0588"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12945"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1992382"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011436344"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.050542"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.081927"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.187"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.04.045"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250802017715"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1154"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.079507.122"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.01.008"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku531"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0420-5"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3361-3366.2005"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01366-07"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00005-16"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2012.667072"},{"issue":"1","key":"e_1_2_10_41_1","first-page":"51","article-title":"The discovery and development of a potent antiviral drug, entecavir, for the treatment of chronic hepatitis B","volume":"1","author":"Tang H","year":"2013","journal-title":"J Clin Transl Hepatol"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006293304"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250902877680"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.087098"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-024-00980-9"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010746"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2017.08.012"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2023.0011"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2022.2112175"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.018747"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12538"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T21:51:59Z","timestamp":1744062719000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/cpdd.1518"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1518","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]},"assertion":[{"value":"2024-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}