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- Publisher Website: 10.1016/j.jhep.2023.05.023
- Scopus: eid_2-s2.0-85171195831
- PMID: 37290591
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Article: Evaluation of RNAi Therapeutics VIR-2218 and ALN-HBV for Chronic Hepatitis B: Results From Randomized Clinical Trials
Title | Evaluation of RNAi Therapeutics VIR-2218 and ALN-HBV for Chronic Hepatitis B: Results From Randomized Clinical Trials |
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Authors | Gane, EdLim, Young SukKim, Jae BJadhav, VasantShen, LingBakardjiev, Anna IHuang, Stephen ACathcart, Andrea LLempp, Florian AJanas, Maja MCloutier, Daniel JKaittanis, CharalambosSepp-Lorenzino, LauraHinkle, GregoryTaubel, JorgHaslett, PatrickMilstein, StuartAnglero-Rodriguez, Yesseinia IHebner, Christy MPang, Phillip SYuen, Man Fung |
Keywords | HBV HBV surface antigen siRNA virology |
Issue Date | 1-Oct-2023 |
Publisher | Elsevier |
Citation | Journal of Hepatology, 2023, v. 79, n. 4, p. 924-932 How to Cite? |
Abstract | BACKGROUND & AIMS\nMETHODS\nRESULTS\nCONCLUSIONS\nTRIAL REGISTRATION\nCurrent treatment for chronic hepatitis B virus (cHBV) infection requires lifelong treatment. New therapy aimed towards HBV functional cure would represent a clinically meaningful treatment advancement. ALN-HBV and VIR-2218 (modified from ALN-HBV by Enhanced Stabilization Chemistry Plus technology reducing off-target, seed-mediated binding while maintaining on-target antiviral activity) are investigational RNAi therapeutics that target all major HBV transcripts.\nWe report the safety of single doses of VIR-2218 and ALN-HBV in humanized mice, a cross-study comparison of single doses of VIR-2218 and ALN-HBV safety in human heathy volunteers (n=24 and n=49, respectively), and the antiviral activity of two monthly doses of 20, 50, 100, 200 mg of VIR-2218 (total n=24) vs. placebo (n=8) in participants with cHBV infection.\nIn humanized mice, alanine aminotransferase (ALT) levels were markedly lower following administration with VIR-2218 compared with ALN-HBV. In healthy volunteers, posttreatment ALT elevations occurred in 28% of participants receiving ALN-HBV compared with none in those receiving VIR-2218. In participants with cHBV infection, VIR-2218 was associated with dose-dependent reductions in hepatitis B surface antigen (HBsAg). The greatest mean reduction of HBsAg at Week 20 in participants receiving 200 mg was 1.65 log IU/mL. The HBsAg reduction was maintained at 0.87 log IU/mL at Week 48. No participants had serum HBsAg loss or hepatitis B surface antibody seroconversion.\nVIR-2218 demonstrated an encouraging hepatic safety profile in preclinical and clinical studies as well as dose-dependent HBsAg reductions in patients with cHBV infection. These data support future studies with VIR-2218 as part of combination regimens with a goal of HBV functional cure. |
Persistent Identifier | http://hdl.handle.net/10722/347962 |
ISSN | 2023 Impact Factor: 26.8 2023 SCImago Journal Rankings: 9.857 |
DC Field | Value | Language |
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dc.contributor.author | Gane, Ed | - |
dc.contributor.author | Lim, Young Suk | - |
dc.contributor.author | Kim, Jae B | - |
dc.contributor.author | Jadhav, Vasant | - |
dc.contributor.author | Shen, Ling | - |
dc.contributor.author | Bakardjiev, Anna I | - |
dc.contributor.author | Huang, Stephen A | - |
dc.contributor.author | Cathcart, Andrea L | - |
dc.contributor.author | Lempp, Florian A | - |
dc.contributor.author | Janas, Maja M | - |
dc.contributor.author | Cloutier, Daniel J | - |
dc.contributor.author | Kaittanis, Charalambos | - |
dc.contributor.author | Sepp-Lorenzino, Laura | - |
dc.contributor.author | Hinkle, Gregory | - |
dc.contributor.author | Taubel, Jorg | - |
dc.contributor.author | Haslett, Patrick | - |
dc.contributor.author | Milstein, Stuart | - |
dc.contributor.author | Anglero-Rodriguez, Yesseinia I | - |
dc.contributor.author | Hebner, Christy M | - |
dc.contributor.author | Pang, Phillip S | - |
dc.contributor.author | Yuen, Man Fung | - |
dc.date.accessioned | 2024-10-04T00:30:37Z | - |
dc.date.available | 2024-10-04T00:30:37Z | - |
dc.date.issued | 2023-10-01 | - |
dc.identifier.citation | Journal of Hepatology, 2023, v. 79, n. 4, p. 924-932 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | http://hdl.handle.net/10722/347962 | - |
dc.description.abstract | <p>BACKGROUND & AIMS\nMETHODS\nRESULTS\nCONCLUSIONS\nTRIAL REGISTRATION\nCurrent treatment for chronic hepatitis B virus (cHBV) infection requires lifelong treatment. New therapy aimed towards HBV functional cure would represent a clinically meaningful treatment advancement. ALN-HBV and VIR-2218 (modified from ALN-HBV by Enhanced Stabilization Chemistry Plus technology reducing off-target, seed-mediated binding while maintaining on-target antiviral activity) are investigational RNAi therapeutics that target all major HBV transcripts.\nWe report the safety of single doses of VIR-2218 and ALN-HBV in humanized mice, a cross-study comparison of single doses of VIR-2218 and ALN-HBV safety in human heathy volunteers (n=24 and n=49, respectively), and the antiviral activity of two monthly doses of 20, 50, 100, 200 mg of VIR-2218 (total n=24) vs. placebo (n=8) in participants with cHBV infection.\nIn humanized mice, alanine aminotransferase (ALT) levels were markedly lower following administration with VIR-2218 compared with ALN-HBV. In healthy volunteers, posttreatment ALT elevations occurred in 28% of participants receiving ALN-HBV compared with none in those receiving VIR-2218. In participants with cHBV infection, VIR-2218 was associated with dose-dependent reductions in hepatitis B surface antigen (HBsAg). The greatest mean reduction of HBsAg at Week 20 in participants receiving 200 mg was 1.65 log IU/mL. The HBsAg reduction was maintained at 0.87 log IU/mL at Week 48. No participants had serum HBsAg loss or hepatitis B surface antibody seroconversion.\nVIR-2218 demonstrated an encouraging hepatic safety profile in preclinical and clinical studies as well as dose-dependent HBsAg reductions in patients with cHBV infection. These data support future studies with VIR-2218 as part of combination regimens with a goal of HBV functional cure.</p> | - |
dc.language | eng | - |
dc.publisher | Elsevier | - |
dc.relation.ispartof | Journal of Hepatology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | HBV | - |
dc.subject | HBV surface antigen | - |
dc.subject | siRNA | - |
dc.subject | virology | - |
dc.title | Evaluation of RNAi Therapeutics VIR-2218 and ALN-HBV for Chronic Hepatitis B: Results From Randomized Clinical Trials | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.jhep.2023.05.023 | - |
dc.identifier.pmid | 37290591 | - |
dc.identifier.scopus | eid_2-s2.0-85171195831 | - |
dc.identifier.volume | 79 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 924 | - |
dc.identifier.epage | 932 | - |
dc.identifier.issnl | 0168-8278 | - |