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Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern.
Mazzaferri, Fulvia; Mirandola, Massimo; Savoldi, Alessia; De Nardo, Pasquale; Morra, Matteo; Tebon, Maela; Armellini, Maddalena; De Luca, Giulia; Calandrino, Lucrezia; Sasset, Lolita; D'Elia, Denise; Sozio, Emanuela; Danese, Elisa; Gibellini, Davide; Monne, Isabella; Scroccaro, Giovanna; Magrini, Nicola; Cattelan, Annamaria; Tascini, Carlo; Tacconelli, Evelina.
  • Mazzaferri F; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Mirandola M; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Savoldi A; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • De Nardo P; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Morra M; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Tebon M; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Armellini M; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • De Luca G; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Calandrino L; Infectious Disease Unit, Padova University Hospital, Padua, Italy.
  • Sasset L; Infectious Disease Unit, Padova University Hospital, Padua, Italy.
  • D'Elia D; Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
  • Sozio E; Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
  • Danese E; Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.
  • Gibellini D; Microbiology and Virology Unit, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • Monne I; Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Scroccaro G; Direzione Farmaceutico, Protesica, Dispositivi Medici, Regione del Veneto, Venice, Italy.
  • Magrini N; Italian Medicines Agency, Rome, Italy.
  • Cattelan A; Infectious Disease Unit, Padova University Hospital, Padua, Italy.
  • Tascini C; Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
  • Tacconelli E; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Elife ; 112022 11 22.
Article in English | MEDLINE | ID: covidwho-2217487
ABSTRACT

Background:

Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC.

Methods:

The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions.

Results:

Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01).

Conclusions:

Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn.

Funding:

This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number NCT05205759.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: ELife.79639

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: ELife.79639