| Title: |
Safety and efficacy of REP 2139-Mg in patients with HDV-related advanced liver disease in an international compassionate access program |
| Authors: |
Stern, Christiane; Loustaud-Ratti, Véronique; Yurdaydin, Cihan; Brancaccio, G; Jachs, Mathias; Reiberger, Thomas; Bardou-Jacquet, Edouard; Métivier, Sophie; Alric, Laurent; Colombain, Léa; Meszaros, Magdalena; Mathurin, Philippe; Yardeni, David; Etzion, Ohad; Neumann-Haefelin, Christoph; Douglas, Mark; Poulin, Sébastien; Bazinet, Michel; Metin, R.Olga; Vitale, Alessandro; Gaeta, Giovanni Battista; Schwarz, Michael; Ben Ali, Souad; Ursic-Bedoya, José; Testoni, Barbara; Zoulim, Fabien; Plissonnier, Marie‐laure; Levrero, Massimo; Paradis, Valérie; Francois, Sandrine; de Freitas Lázaro Emediato, Carla Cecília; Kaysin, Furkan; Lecomte, Laurence; Morvan, Christopher; Schramko, Jocelyn; Bondezi, Kindness; Baril, Marie-Éve; Brichler, Ségolène; Gerber, Athenaïs; Gordien, Emmanuel; Mackiewicz, Vincent; Dahari, Harel; Svicher, Valentina; Chevaliez, Stéphane; Vaillant, Andrew; Bourlière, Marc |
| Contributors: |
Centre Hospitalier de Versailles André Mignot (CHV); Université de Limoges (UNILIM); Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT); CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST); Université de Limoges (UNILIM)-Université de Limoges (UNILIM); Koç University; Link Campus University Roma = Università degli Studi Link Roma; Medical University of Vienna = Medizinische Universität Wien (MedUni Vienna); Centre Hospitalier Universitaire Rennes; Nutrition, Métabolismes et Cancer (NuMeCan); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Centre Hospitalier Saint Jean de Perpignan (CH Perpignan); CHU Montpellier = Montpellier University Hospital; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Soroka University Medical Center Beer Sheva, Israel; University Hospital of Cologne Cologne; Westmead Hospital Sydney; Università degli Studi di Padova = University of Padua (Unipd); Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli; Hôpital Saint-Joseph Marseille; Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD); Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Hospices Civils de Lyon (HCL); Physiopathologie et Traitement des Maladies Hépatiques (PaThLiv); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM); Hôpital Beaujon AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Hôpital Avicenne AP-HP; AP-HP - Hôpital Bichat - Claude Bernard Paris; Loyola University Chicago; Università degli Studi di Roma Tor Vergata Roma, Italia = University of Rome Tor Vergata Rome, Italy = Université de Rome Tor Vergata Rome, Italie; CHU Henri Mondor Créteil; Groupe Henri Mondor-Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Replicor.inc Montréal; No funding specific to this compassionate cohort was received. HD is supported by U.S. NIH grant R01AI146917. |
| Source: |
ISSN: 0168-8278. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2025 |
| Collection: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| Subject Terms: |
REP 2139; antiviral agents; cirrhosis; hepatitis D; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology |
| Description: |
International audience ; Background & aims: REP 2139-Mg (REP), a nucleic acid polymer, blocks HBV subviral particle assembly and HDV replication. We hereby report results of REP treatment in HDV patients in a compassionate access program (NCT05683548).Methods: Thirty-three HDV patients with advanced chronic liver disease (ACLD) received REP 250mg weekly subcutaneously (SC) plus nucleotide analog for a scheduled 48-weeks duration. Pegylated interferon-α (pegIFN) 45-180ug weekly was added in 20 patients without contraindications. Safety and efficacy were monitored regularly, and intra-hepatic markers performed in one liver explant.Results: Among the 33 patients (age 21-69 years, 21 males), 85% (28/33) had previous treatment failure and 6 had decompensated cirrhosis (ascites n=5). Suboptimal response to REP was rescued with dose modifications [250mg intravenously (IV), or 500mg SC or IV] and/or therapy extension in 21 patients. At the end of therapy (EoT), HDV-RNA declined by >2log10 in 70% (23/33) and was undetectable in 58% (19/33). HBsAg loss occurred in 27% (9/33). In the 28 patients with available follow-up, HDV-RNA and HBsAg remained undetectable in 46% (13/28) and 18% (5/28) respectively. ALT normalized in 50% (14/28). Response was similar with or without pegIFN. Ascites improved in 2/5 patients. Three patients underwent liver transplantation while receiving REP, with no complications. One liver explant analysis showed undetectable HDV-RNA and HDAg and very low levels of intra-hepatic cccDNA activity and HBsAg. No REP-related serious adverse events were reported.Conclusions: REP treatment was safe and effective in HDV patients with ACLD. REP may even induce HDV sustained virological response and HBV functional cure independent of combination with pegIFN. Clinical benefits may also be observed in patients with decompensated cirrhosis.Impact and implications: No antiviral treatment is approved for chronic hepatitis D (CHD) patients with decompensated cirrhosis or in patients who have failed previous ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41205755; PUBMED: 41205755 |
| DOI: |
10.1016/j.jhep.2025.10.029 |
| Availability: |
https://hal.science/hal-05418962; https://hal.science/hal-05418962v1/document; https://hal.science/hal-05418962v1/file/Stern%20et%20al.%20-%202025%20-%20Safety%20and%20efficacy%20of%20REP%202139-Mg%20in%20patients%20with%20HDV-related%20advanced%20liver%20disease%20in%20an%20interna_removed.pdf; https://doi.org/10.1016/j.jhep.2025.10.029 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.DCCCB330 |
| Database: |
BASE |