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| Verfasst von: | Hollnberger, Julius [VerfasserIn]  |
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| | Liu, Yang [VerfasserIn] |
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| | Xu, Simin [VerfasserIn] |
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| | Chang, Silvia [VerfasserIn] |
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| | Martin, Ross [VerfasserIn] |
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| | Manhas, Savrina [VerfasserIn] |
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| | Aeschbacher, Thomas [VerfasserIn] |
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| | Han, Bin [VerfasserIn] |
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| | Yazdi, Tahmineh [VerfasserIn] |
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| | May, Lindsey [VerfasserIn] |
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| | Han, Dong [VerfasserIn] |
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| | Shornikov, Alex [VerfasserIn] |
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| | Flaherty, John [VerfasserIn] |
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| | Manuilov, Dmitry [VerfasserIn] |
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| | Suri, Vithika [VerfasserIn] |
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| | Asselah, Tarik [VerfasserIn] |
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| | Lampertico, Pietro [VerfasserIn] |
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| | Wedemeyer, Heiner [VerfasserIn] |
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| | Aleman, Soo [VerfasserIn] |
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| | Richards, Christopher [VerfasserIn] |
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| | Mateo, Roberto [VerfasserIn] |
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| | Maiorova, Evguenia [VerfasserIn] |
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| | Cihlar, Tomas [VerfasserIn] |
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| | Mo, Hongmei [VerfasserIn] |
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| | Urban, Stephan [VerfasserIn] |
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| Titel: | No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta |
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| Verf.angabe: | Julius Hollnberger, Yang Liu, Simin Xu, Silvia Chang, Ross Martin, Savrina Manhas, Thomas Aeschbacher, Bin Han, Tahmineh Yazdi, Lindsey May, Dong Han, Alex Shornikov, John Flaherty, Dmitry Manuilov, Vithika Suri, Tarik Asselah, Pietro Lampertico, Heiner Wedemeyer, Soo Aleman, Christopher Richards, Roberto Mateo, Evguenia Maiorova, Tomas Cihlar, Hongmei Mo, Stephan Urban |
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| E-Jahr: | 2023 |
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| Jahr: | September 2023 |
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| Umfang: | 9 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 27. April 2023, Artikelversion: 19. August 2023 ; Gesehen am 07.12.2023 |
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| Titel Quelle: | Enthalten in: Journal of hepatology |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1985 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 79(2023), 3 vom: Sept., Seite 657-665 |
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| ISSN Quelle: | 1600-0641 |
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| Abstract: | Background & Aims - Bulevirtide (BLV) is a HDV/HBV entry inhibitor that is associated with virologic response (responders, HDV-RNA undetectable or ≥2 log10 IU/ml decrease from baseline) in >50% of patients after a 24-week treatment. However, some patients only achieve a <1 log10 IU/ml decline in HDV-RNA after the 24-week treatment (non-responders). Here, we report a viral resistance analysis in participants receiving BLV monotherapy who were non-responders or experienced virologic breakthrough (VB, i.e., two consecutive increases in HDV-RNA of ≥1 log10 IU/ml from nadir or two consecutive HDV-RNA detectable results if previously undetectable) from the phase II MYR202 and phase III MYR301 study. - Methods - Deep-sequencing of the BLV-corresponding region in HBV PreS1 and of the HDV HDAg gene, as well as in vitro phenotypic testing, were performed for the participant with VB (n = 1) and non-responders (n = 20) at baseline (BL) and Week 24 (WK24). - Results - No amino acid exchanges associated with reduced susceptibility to BLV within the BLV-corresponding region or within HDAg were identified in isolates from any of the 21 participants at BL or at WK24. Although variants (HBV n = 1; HDV n = 13) were detected at BL in some non-responders or in the participant with VB, none were associated with reduced sensitivity to BLV in vitro. Furthermore, the same variant was detected in virologic responders. A comprehensive phenotypic analysis demonstrated that the BLV EC50 values from 116 BL samples were similar across non-responders, partial responders (HDV RNA decline ≥1 but <2 log10 IU/ml), and responders regardless of the presence of HBV and/or HDV polymorphisms. - Conclusions - No amino acid substitutions associated with reduced sensitivity to BLV monotherapy were detected at BL or WK24 in non-responders or the participant with VB after 24-week BLV treatment. - Impact and Implications - This is the first study investigating the development of resistance in patients treated with BLV. Excluding resistance to BLV as an explanation for an insufficient decrease in HDV-RNA levels during BLV therapy is an important finding for patients, clinicians, and researchers. It demonstrates that BLV has a high barrier to resistance, indicating it is safe and suitable for long-term treatment, although long-term surveillance for resistance should be performed. Our results hint at other still unknown mechanisms as an explanation for the persistence of serum HDV-RNA during inhibition of viral entry. - Clinical trial numbers - NCT03546621 and NCT03852719. |
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| DOI: | doi:10.1016/j.jhep.2023.04.027 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.jhep.2023.04.027 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S0168827823003136 |
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| | DOI: https://doi.org/10.1016/j.jhep.2023.04.027 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Antiviral agent |
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| | Antiviral therapy |
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| | Bulevirtide |
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| | Chronic Hepatitis Delta |
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| | Clinical trial |
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| | Entry-inhibitor |
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| | Virologic resistance |
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| K10plus-PPN: | 1872285023 |
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| Verknüpfungen: | → Zeitschrift |
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No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta / Hollnberger, Julius [VerfasserIn]; September 2023 (Online-Ressource)
