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Manish C Choudhary, PhD
Pronouns
He/Him/His
Job Title
Research Fellow
Academic Rank
Research Fellow
Department
Medicine
Authors
Manish C. Choudhary, Rinki Deo, Teresa H. Evering, Kara W. Chew, James Regan, James P. Flynn, Mark J. Giganti, Carlee Moser, Justin Ritz, David Alain Wohl, Judith S. Currier, Joseph J. Eron , David Margolis, Qing Zhu, Lijie Zhong, Li Yan, Michael D. Hughes, Davey Smith, Eric S. Daar, Jonathan Z. Li for the ACTIV-2/A5401 Study Team
Principal Investigator
Jonathan Z. Li
Research Category: COVID-19
Tags
Background: Amubarvimab and romlusevimab are anti-SARS-CoV-2 monoclonal antibodies (mAbs) that demonstrated significantly reduced risk of hospitalizations or death in the ACTIV-2/A5401 phase 2/3 trial. We evaluated antiviral efficacy of amubarvimab and romlusevimab and assessed risk of treatment-emergent mAb resistance.
Methods: The study population included 789 participants who received placebo (n=400) or amubarvimab plus romlusevimab (n=389). We compared rates of viral decay and resistance emergence with single versus dual-active mAbs by categorizing participants harboring variants sensitive to amubarvimab alone (Delta, Epsilon, Lambda, Mu) versus those sensitive to both mAbs (Alpha, Beta, Gamma, Others).
Results: The most common SARS-CoV-2 variant in the study population was Delta (26%) followed by Gamma (19%), Alpha (12%), and Epsilon (10%). Compared to treatment with a single active mAb, treatment with dual active mAbs led to faster viral clearance at study day 3 (p=0.0001) and day 7 (p=0.003). Treatment-emergent resistance mutations were significantly more likely after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, p=0.0008). Higher frequency of mAb resistance was detected with single active mAb treatment versus dual mAb treatment (7.2% vs 1.1%, p=0.007). Participants with emerging mAb resistance had significantly higher pre-treatment SARS-CoV-2 nasal viral RNA levels.
Conclusions: Dual active mAb therapy led to significantly faster rates of viral decay and lower risk of mAb resistance.
Background: Amubarvimab and romlusevimab are anti-SARS-CoV-2 monoclonal antibodies (mAbs) that significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 phase 2/3 trial.
Methods: We compared rates of viral decay and resistance emergence with single versus dual-active mAbs by categorizing participants harboring variants sensitive to amubarvimab alone (Delta, Epsilon, Lambda, Mu) versus those sensitive to both mAbs (Alpha, Beta, Gamma, Others).
Results: Treatment with two active mAbs led to faster viral clearance at study days 3 and 7, compared to treatment with a single active mAb. The emergence of resistance mutations was significantly more likely after single active mAb treatment compared to treatment with two active mAbs.
Conclusion: Dual active mAb therapy for COVID-19 led to faster viral clearance and a lower risk of emergence of drug resistance.
