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Randomized Controlled Trial
. 2022 Nov 22:11:e79639.
doi: 10.7554/eLife.79639.

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

Fulvia Mazzaferri  1 , Massimo Mirandola  1 , Alessia Savoldi  1 , Pasquale De Nardo  1 , Matteo Morra  1 , Maela Tebon  1 , Maddalena Armellini  1 , Giulia De Luca  1 , Lucrezia Calandrino  2 , Lolita Sasset  2 , Denise D'Elia  3 , Emanuela Sozio  3 , Elisa Danese  4 , Davide Gibellini  5 , Isabella Monne  6 , Giovanna Scroccaro  7 , Nicola Magrini  8 , Annamaria Cattelan  2 , Carlo Tascini  3 ; MANTICO Working Group; Evelina Tacconelli  1
Collaborators, Affiliations
Randomized Controlled Trial

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

Fulvia Mazzaferri et al. Elife. .

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.

Keywords: Omicron; bamlanivimab/etesevimab; casirivimab/imdevimab; early covid-19; human; medicine; monoclonal antibody; sotrovimab.

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Conflict of interest statement

FM, MM, AS, PD, MM, MT, MA, GD, LC, DD, ES, ED, DG, IM, GS, NM, ET No competing interests declared, LS Lolita Sasset has served as a paid consultant to Abbvie, Janssen, MSD, Gilead Sciences, Janssen, MSD and ViiV Healthcare; she does not have any financial competing interests with this study, AC Annamaria Cattelan has served as a paid consultant to Abbvie, Janssen, MSD, and received research fundings from Gilead Sciences, Janssen, MSD and ViiV Healthcare; she does not have any financial competing interests with this study, CT Carlo Tascini has received grants from Correvio, Biotest, Biomerieux, Gilead, Angelini, MSD, Pfizer, Thermofisher, Zambon, Shionogi, Avir Pharma and Hikma outside the submitted work in the last two years

Figures

Figure 1.
Figure 1.. Flow diagram of the progress through the phases of the MANTICO trial according to the CONSORT statement.
Figure 2.
Figure 2.. Time to symptom resolution by type of treatment in the study population infected with Delta (A) and Omicron (B).
See this image and copyright information in PMC

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