{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:01:30Z","timestamp":1791918090328,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Current treatment options for chronic HBV infection are suboptimal in that they fail to suppress HBsAg levels. ALG\u2010020572 is an antisense oligonucleotide designed to reduce viral protein synthesis through degradation of HBV mRNA. ALG\u2010020572\u2010401 was a double\u2010blind, randomized, placebo\u2010controlled trial consisting of two parts. Part 1 (single\u2010ascending doses) evaluated the pharmacokinetics, safety and tolerability of single doses of ALG\u2010020572 or placebo in healthy participants. In Part 2 (multiple dosing), participants with non\u2010cirrhotic HBeAg\u2010negative, virologically suppressed chronic HBV infection were administered up to 7 doses of ALG\u2010020572 to evaluate safety, pharmacokinetics and antiviral activity. In Part 1, 32 participants were randomized to ALG 020572 or placebo. Single doses of ALG\u2010020572 up to 480\u2009mg were well tolerated. The most common treatment\u2010emergent adverse event reported was injection site reaction. ALG\u2010020572 was rapidly absorbed and plasma exposures increased with dose. In Part 2, 8 participants with non\u2010cirrhotic HBeAg\u2010negative virologically suppressed chronic hepatitis B infection were enrolled and received up to 7 doses of ALG\u2010020572. The study was prematurely discontinued after 4 participants experienced significant alanine aminotransferase elevations that were subsequently attributed to drug\u2010induced liver injury. Single doses of ALG\u2010020572 demonstrated a favourable pharmacokinetic and safety profile in healthy participants. Unexpectedly, ALG\u2010020572 was poorly tolerated in participants with chronic HBV infection, resulting in the early termination of the study and further development of ALG\u2010020572 due to idiosyncratic drug\u2010induced liver injury, suggesting caution is required in the development of this class of drugs.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Registered at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                    : NCT0500102\n                  <\/jats:p>","DOI":"10.1111\/jvh.70224","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:08:03Z","timestamp":1787645283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>ALG<\/scp>\n                    \u2010020572, an Antisense Oligonucleotide for the Treatment of Chronic Hepatitis B Virus Infection Discontinued for Drug\u2010Induced Liver Injury"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-828X","authenticated-orcid":false,"given":"Kosh","family":"Agarwal","sequence":"first","affiliation":[{"name":"Institute of Liver Studies King's College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-9169","authenticated-orcid":false,"given":"Dan","family":"Forton","sequence":"additional","affiliation":[{"name":"NIHR St. George's Clinical Research Facility St. George's University Hospitals  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-6508","authenticated-orcid":false,"given":"Yoh","family":"Zen","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies King's College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Aligos Therapeutics, Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tse\u2010I","family":"Lin","sequence":"additional","affiliation":[{"name":"Aligos Belgium BV  Mechelen Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kha","family":"Le","sequence":"additional","affiliation":[{"name":"Aligos Therapeutics, Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2290-5428","authenticated-orcid":false,"given":"Sushmita","family":"Chanda","sequence":"additional","affiliation":[{"name":"Aligos Therapeutics, Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Blatt","sequence":"additional","affiliation":[{"name":"Aligos Therapeutics, Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7647-2456","authenticated-orcid":false,"given":"John","family":"Fry","sequence":"additional","affiliation":[{"name":"Aligos Therapeutics, Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-7955","authenticated-orcid":false,"given":"Ed","family":"Gane","sequence":"additional","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.03.018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2016.0045"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050417"},{"key":"e_1_2_10_5_1","volume-title":"Guidelines for the Prevention, Diagnosis, Care and Treatment for People With Chronic Hepatitis B Infection","author":"World Health Organization (WHO)","year":"2024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31030"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S240472"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13307"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.01.044"},{"key":"e_1_2_10_11_1","unstructured":"Pegasys Summary of Product Characteristics \u201cLoba Biotech GmbH \u201dPegasys Peg\u2010Interferon Alfa\u20102a (europa.eu)."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14837"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i21.2727"},{"key":"e_1_2_10_14_1","first-page":"S49","article-title":"ALG\u2010020572, a Next Generation Hepatitis B Virus (HBV) Antisense Oligonucleotide (ASO) With Bridged Nucleic Acid Chemistry, Has a Significantly Improved Preclinical Profile","volume":"15","author":"Hong J.","year":"2021","journal-title":"Hepatology International"},{"key":"e_1_2_10_15_1","first-page":"503A","article-title":"ALG\u2010020572, a GalNAc\u2010Conjugated Antisense Oligonucleotide, Demonstrates In\u00a0Vivo Efficacy and Favorable Preclinical Profile for the Treatment of Chronic Hepatitis B","volume":"74","author":"Gupta K.","year":"2021","journal-title":"Hepatology"},{"key":"e_1_2_10_16_1","unstructured":"US Department of Health and Human Services \u201cNational Institutes of Health National Institute of Allergy and Infectious Diseases Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 \u201d(2017) https:\/\/rsc.niaid.nih.gov\/sites\/default\/files\/daidsgradingcorrectedv21.pdf."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.136"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.6008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110418"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.4065\/75.12.1284"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210027"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(22)02041-4"},{"key":"e_1_2_10_23_1","unstructured":"Arbutus Press Release \u201cArbutus Announces Decision to Discontinue Development of AB\u2010506 an Oral Capsid Inhibitor for the Treatment of Chronic Hepatitis B \u201d(2019) https:\/\/investor.arbutusbio.com\/news\u2010releases\/news\u2010release\u2010details\/arbutus\u2010announces\u2010decision\u2010discontinue\u2010development\u2010ab\u2010506\u2010oral."},{"key":"e_1_2_10_24_1","volume-title":"Development of Hepatitis B Virus Inhibitor AB\u2010836 Terminated due to Safety Concerns","author":"Arbutus Press Release","year":"2022"},{"key":"e_1_2_10_25_1","volume-title":"Kastle Therapeutics","author":"Kynamro (Mipomersen Sodium) Injection Prescribing Information Insert","year":"2016"},{"key":"e_1_2_10_26_1","unstructured":"US FDA \u201cFull Prescribing Information for Tegsedi (Inotersen) for Injection \u201d(2019)."}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.70224","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.70224","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.70224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:25:47Z","timestamp":1787829947000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.70224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jvh.70224"],"URL":"https:\/\/doi.org\/10.1111\/jvh.70224","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70224"}}