Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in hospitalized COVID-19 patients: long-term results from the DisCoVeRy trial

Clément R. Massonnaud; Nathan Peiffer-Smadja; Pascal Poignard; Simon Jamard; François Goehringer; François Danion; Jean Reignier; Nathalie de Castro; Denis Garot; Eva Larranaga Lapique; Karine Lacombe; Violaine Tolsma; Emmanuel Faure; Denis Malvy; Thérèse Staub; Johan Courjon; France Cazenave-Roblot; Anne Ma Dyrhol Riise; Paul Leturnier; Guillaume Martin-Blondel; Claire Roger; Karolina Akinosoglou; Vincent Le Moing; Lionel Piroth; Pierre Sellier; Xavier Lescure; Marius Trøseid; Philippe Clevenbergh; Olav Dalgard; Sébastien Gallien; Marie Gousseff; Paul Loubet; Fanny Vardon-Bounes; Clotilde Visée; Leila Belkhir; Élisabeth Botelho-Nevers; André Cabié; Anastasia Kotanidou; Fanny Lanternier; Elisabeth Rouveix-Nordon; Susana Silva; Guillaume Thiery; Guislaine Carcelain; Alpha Diallo; Noémie Mercier; Vida Terzić; Maude Bouscambert-Duchamp; Alexandre Gaymard; Grégory Destras; Laurence Josset; Drifa Belhadi; Nicolas Billard; Jérémie Guedj; Thi-Hong-Lien Han; Sandrine Couffin-Cadiergues; Aline Dechanet; Christelle Delmas; Hélène Esperou; Claire Fougerou-Leurent; Soizic Le Mestre; Annabelle Métois; Marion Noret; Isabelle Bally; Sebastián Dergan-Dylon; Sarah Tubiana; Ouifiya Kalif; Nathalie Bergaud; Benjamin Leveau; Joe Eustace; Richard Greil; Edit Hajdu; Monika Halanova; Jose-Artur Paiva; Anna Piekarska; Jesus Rodriguez Baño; Kristian Tonby; Milan Trojánek; Sotirios Tsiodras; Serhat Unal; Charles Burdet; Dominique Costagliola; Yazdan Yazdanpanah; France Mentré; Florence Ader; Maya Hites; the DisCoVeRy study group

doi:10.1016/j.cmi.2025.12.014

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Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in hospitalized COVID-19 patients: long-term results from the DisCoVeRy trial

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Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in hospitalized COVID-19 patients: long-term results from the DisCoVeRy trial

Clément R. Massonnaud, Nathan Peiffer-Smadja, Pascal Poignard, Simon Jamard, François Goehringer, François Danion, Jean Reignier, Nathalie de Castro, Denis Garot, Eva Larranaga Lapique, …

Clinical microbiology and infection

20/12/2025

DOI: https://doi.org/10.1016/j.cmi.2025.12.014

PMID: 41429349

Résumé

To report long-term clinical efficacy, safety, pharmacokinetics, immunogenicity and seroneutralization results of AZD7442 (monoclonal antibodies tixagevimab-cilgavimab) in hospitalized COVID-19 patients. In this phase 3, double-blind, randomized, multicenter trial, hospitalized adults with PCR-confirmed SARS-CoV-2 infection were randomized 1:1 to receive AZD7442 or placebo, and followed-up until day 456, with repeated blood sample collections until day 365. Clinical endpoints included clinical status, mortality, rehospitalization, SARS-CoV-2 reinfection, and adverse events. Antidrug antibodies (ADA) and serum drug concentrations were measured. Analyses were performed on the modified intention-to-treat populations, defined as participants who actually received the intervention. Between April 28, 2021, and June 23, 2022, 237 participants were randomized to AZD7442 (n=127) or placebo (n=110), and 123 participants actually received AZD7442. Participants were infected with pre-Omicron variants in 58.8% (133/226) of cases, versus 33.2% (75/226) of Omicron BA1, BA2, or BA5, and 8% (18/226) missing data. There was no significant difference in the distribution of the 7-point ordinal scale between the AZD7442 and placebo groups, either on day 15 (primary endpoint), OR=0.93 [0.54-1.61], P=0.81, or any other time point. Significantly more rehospitalizations occurred between discharge and day 456 among participants who received AZD7442 in the global mITT population (OR=2.04 [1.03-4.05], P=0.04), but not in the antigen-positive mITT population (OR=1.78 [0.80-3.94], P=0.15). No significant differences were observed in mortality, SARS-CoV-2 reinfection, or adverse events. In the AZD7442 group, 12/87 participants (13.8%) had treatment-emergent ADA versus 5/69 (7.2%) in the placebo group (OR=2.02 [0.66-6.14], P=0.21). Serum drug concentrations were detectable up to day 365 for all sampled participants (35/35). Neutralizing antibody titres were significantly higher in the AZD7442 group up to day 180. AZD7442 did not demonstrate any clinical benefit and was safe up to 15 months. This study also provides valuable data on the pharmacokinetics, immunogenicity, and neutralizing activity of AZD7442 in hospitalized COVID-19 patients.

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Titre: Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in hospitalized COVID-19 patients: long-term results from the DisCoVeRy trial
Créateurs - sans rôle: Clément R. Massonnaud - Assistance Publique – Hôpitaux de Paris
Nathan Peiffer-Smadja - Université de Paris, IAME, INSERM, F-75018 Paris, France
Pascal Poignard - Université Grenoble Alpes
Simon Jamard - Centre Hospitalier Universitaire de Tours
François Goehringer - Université de Lorraine, CHRU de Nancy, Service des Maladies Infectieuses et Tropicales, F-54000 Nancy, France
François Danion - . Hôpitaux Universitaires de Strasbourg, Département de maladies infectieuses et tropicales, F- 67091 Strasbourg. France
Jean Reignier - CHU de Nantes, Service de Médecine Intensive et Réanimation, Université de Nantes, F-44093 Nantes, France
Nathalie de Castro - Inserm
Denis Garot - CHRU Tours, Service de Médecine Intensive Réanimation, F-37044 Tours, France
Eva Larranaga Lapique - Université Libre de Bruxelles
Karine Lacombe - Sorbonne Université, Inserm, Institut Pierre-Louis d’Épidémiologie et de Santé Publique, F-75013, Paris, France
Violaine Tolsma - Centre Hospitalier Annecy Genevois, Service des Maladies Infectieuses et Tropicales, F-74374 Annecy, France
Emmanuel Faure - CHU Lille, Service Universitaire de maladies infectieuses, F-59000 Lille, France
Denis Malvy - Department of Infectious Diseases and Tropical Medicine, CHU Bordeaux, Bordeaux, France
Thérèse Staub - Centre Hospitalier de Luxembourg
Johan Courjon - Université Côte d’Azur, CHU Nice, Infectious Disease Unit, Nice, France
France Cazenave-Roblot - Inserm
Anne Ma Dyrhol Riise - Department of Infectious Diseases, Oslo University Hospital, 0424 Oslo, Norway
Paul Leturnier - Department of Infectious Diseases, Hôtel-Dieu University Hospital, University Hospital of Nantes, Nantes, France
Guillaume Martin-Blondel - CHU de Toulouse, Service des maladies infectieuses et Tropicales, F-31320 Toulouse, France
Claire Roger - Department of Anesthesiology, Critical Care Pain, and Emergency Medicine, Nimes University Hospital, Nimes, France
Karolina Akinosoglou - Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, Patras, Greece
Vincent Le Moing - CHU de Montpellier, Service des Maladies Infectieuses et Tropicales, F- 34295 Montpellier, France
Lionel Piroth - CHU Dijon Bourgogne
Pierre Sellier - Infectious Diseases Department, Lariboisière Hospital, AP-HP, Paris, France
Xavier Lescure - Université de Paris, IAME, INSERM, F-75018 Paris, France
Marius Trøseid - Oslo University Hospital
Philippe Clevenbergh - Centre Hospitalier Universitaire Brugmann
Olav Dalgard - Akershus University Hospital
Sébastien Gallien - APHP, Hôpital Henri Mondor, Département de maladies infectieuses, F-94000 Créteil, France
Marie Gousseff - Centre hospitalier Bretagne Atlantique
Paul Loubet - Infectious and Tropical Diseases Department, Nimes University Hospital, Nimes, France
Fanny Vardon-Bounes - CHU de Toulouse, Département d’anesthésie et de soins intensifs, F- 31300 Toulouse, France
Clotilde Visée - Department of Infectious Disease, Centre Hospitalier Régional Mons-Hainaut/Groupe Jolimont, Mons Belgium/Groupe Helora, Mons, Belgium
Leila Belkhir - Department of Internal Medicine and Infectious Diseases, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
Élisabeth Botelho-Nevers - CHU de Saint-Etienne, Service d’Infectiologie, F- 42055 Saint-Etienne, France
André Cabié - PCCEI, Univ Montpellier, Univ Antilles, Inserm, EFS, F- 34394 Montpellier, France
Anastasia Kotanidou - National and Kapodistrian University of Athens
Fanny Lanternier - Infectious Diseases Unit, Necker-Enfants Malades University Hospital, AP-HP, Paris, France
Elisabeth Rouveix-Nordon - AP-HP, Hôpital Ambroise-Paré, Service de Maladies Infectieuses et Tropicales, Boulogne-Billancourt, France
Susana Silva - EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, no 135, 4050-600, Porto, Portugal
Guillaume Thiery - Centre Hospitalier Universitaire de Saint-Étienne
Guislaine Carcelain - Assistance Publique – Hôpitaux de Paris
Alpha Diallo - ANRS Maladies Infectieuses Emergentes, Paris, France
Noémie Mercier - ANRS Maladies Infectieuses Emergentes, Paris, France
Vida Terzić - Agence Nationale de Recherches sur le Sida et les Hépatites Virales
Maude Bouscambert-Duchamp - Hospices Civils de Lyon
Alexandre Gaymard - Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux de Lyon, Centre National de Référence des virus respiratoires France Sud, F-69317, Lyon, France
Grégory Destras - Hospices Civils de Lyon
Laurence Josset - Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux de Lyon, Centre National de Référence des virus respiratoires France Sud, F-69317, Lyon, France
Drifa Belhadi - AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, F-75018 Paris, France
Nicolas Billard - Assistance Publique – Hôpitaux de Paris
Jérémie Guedj - Inserm
Thi-Hong-Lien Han - Assistance Publique – Hôpitaux de Paris
Sandrine Couffin-Cadiergues - Institut de santé publique, Pôle recherche clinique, INSERM, Paris, France
Aline Dechanet - AP-HP, Hôpital Bichat, Unité de recherche clinique, F-75018 Paris, France
Christelle Delmas - Institut de santé publique, Pôle recherche clinique, INSERM, Paris, France
Hélène Esperou - Institut de santé publique, Pôle recherche clinique, INSERM, Paris, France
Claire Fougerou-Leurent - Université Rennes 1
Soizic Le Mestre - Institut de santé publique, Pôle recherche clinique, INSERM, Paris, France
Annabelle Métois - AP-HP, Hôpital Bichat, Unité de recherche clinique, F-75018 Paris, France
Marion Noret - Renarci, Réseau National De Recherche Clinique En Infectiologie, France
Isabelle Bally - Institut de Biologie Structurale
Sebastián Dergan-Dylon - Institut de Biologie Structurale
Sarah Tubiana - Inserm
Ouifiya Kalif - Assistance Publique – Hôpitaux de Paris
Nathalie Bergaud - Hospices Civils de Lyon
Benjamin Leveau - Hospices Civils de Lyon
Joe Eustace - University College Cork
Richard Greil - Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Edit Hajdu - University of Szeged
Monika Halanova - LF UPJŠ - Pavol Jozef Šafárik University in Košice Faculty of Medicine
Jose-Artur Paiva - Centro Hospitalar São João, Emergency and Intensive Care Department, Porto, Portugal
Anna Piekarska - University of Łódź
Jesus Rodriguez Baño - Unidad Clínica de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Seville, Spain
Kristian Tonby - Department of Infectious Diseases, Oslo University Hospital, 0424 Oslo, Norway
Milan Trojánek - Charles University
Sotirios Tsiodras - National and Kapodistrian University of Athens
Serhat Unal - Hacettepe University
Charles Burdet - Assistance Publique – Hôpitaux de Paris
Dominique Costagliola - Sorbonne Université
Yazdan Yazdanpanah - Université de Paris, IAME, INSERM, F-75018 Paris, France
France Mentré - AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, F-75018 Paris, France
Florence Ader - Hôpital de la Croix-Rousse
Maya Hites - Université Libre de Bruxelles
the DisCoVeRy study group
Détails de publication: Clinical microbiology and infection
Éditeur: Elsevier Ltd
Identifiants: 99149019309311
Unité académique: Virulence Bacterienne et Infections Chroniques - VBIC; Recherches translationnelles sur le VIH et les Maladies Infect. Endém. émerg. - TransVIHMI
Langue: English
Type de ressource: Journal article