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Basic Characteristics of Mutations
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Mutation Site
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F23Y |
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Mutation Site Sentence
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Two JNJ‐6379‐treated patients (both HBeAg‐negative, GT‐A and GT‐E, and JNJ‐6379 75 and 150 mg treated, respectively) carried a Y118F baseline polymorphism, while a placebo‐treated patient (HBeAg‐negative, GT‐H) carried a F23Y baseline polymorphism (FC = 6.6 and 5.2, respectively). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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C |
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Standardized Encoding Gene
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C
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Genotype/Subtype
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A;E;H |
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Viral Reference
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X02763
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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Europe;Asia Pacific |
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Literature Information
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PMID
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32579776
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Title
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Virology analysis of chronic hepatitis B virus-infected patients treated for 28 days with JNJ-56136379 monotherapy
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Author
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Verbinnen T,Hodari M,Talloen W,Berke JM,Blue D,Yogaratnam J,Vandenbossche J,Shukla U,De Meyer S,Lenz O
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Journal
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Journal of viral hepatitis
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Journal Info
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2020 Nov;27(11):1127-1137
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Abstract
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Four weeks of once-daily oral JNJ-56136379 (JNJ-6379; 25, 75, 150 or 250 mg), a class-N capsid assembly modulator (CAM-N), was well tolerated with potent antiviral activity in treatment-naive, chronic hepatitis B e antigen-positive and hepatitis B e antigen-negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next-generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ-6379 and/or other CAMs in vitro resistance, and those within the CAM-binding pocket. 31/57 patients had >/= 1 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ-6379 in vitro activity (fold change [FC] in 50% effective concentration <3.0). Two JNJ-6379-treated patients carried a Y118F baseline core polymorphism known to reduce JNJ-6379 activity in vitro (FC = 6.6) and had HBV DNA declines of 2.77 (75 mg) and 2.19 log(10) IU/mL (150 mg) at the end of treatment. One 75 mg JNJ-6379-treated patient had an emerging T109S substitution (FC = 1.8; HBV DNA decline 3.18 log(10) IU/mL). A 25 mg JNJ-6379-treated patient had on-treatment enrichment of Y118F variant (HBV DNA decline 2.13 log(10) IU/mL). In conclusion, baseline polymorphisms and enrichment of substitutions reducing JNJ-6379 in vitro activity were rare, with no consistent impact on virological response during a 4-week phase 1b study. Emergence of resistance to longer treatments of JNJ-6379 will be evaluated in phase 2 studies.
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Sequence Data
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NCT02662712
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