124: Pharmacokinetics & Pharmacodynamics of Casirivimab & Imdevimab in Pregnant Outpatients With COVID-19

Statement of Purpose: Casirivimab and imdevimab (REGEN-COV®) is a combination of two noncompeting human IgG1 monoclonal antibodies (mAbs) that neutralizes susceptible SARS-CoV-2 virus variants, authorized by US FDA for emergency use during the public health emergency prior to the widespread circulation of Omicron variants. REGEN-COV is unlikely to be active against Omicron and subsequent variants. An adaptive Phase 1/2/3 study was conducted (in 2020-2021, prior to the emergence of omicron-lineage variants) to investigate the efficacy, safety and tolerability of single intravenous (IV) infusions of REGEN-COV in outpatients with COVID-19 (NCT04425629). In the Phase 3 portion of this study, pregnant patients were enrolled who received one of the same IV doses (i.e., 1,200 mg or 2,400 mg) used in adult non-pregnant patients. The purpose of this abstract is to report the pharmacokinetic (PK), concentration-response for nasopharyngeal viral load (NP VL) reduction and immunogenicity results in pregnant outpatients with COVID-19.

Description of Methods & Materials: Concentrations of total casirivimab and total imdevimab in serum samples were analyzed for 66 pregnant patients. Anti-casirivimab and anti-imdevimab antibodies (anti-drug antibodies; ADA) were assessed in serum samples from 73 pregnant patients receiving placebo (n=1) or casirivimab and imdevimab (n=72). Casirivimab and imdevimab concentrations in serum for adult pregnant patients were compared with non-pregnant adult patients (n= 2,521). Casirivimab and imdevimab concentrations were also analyzed by trimester of pregnancy at baseline (1 to 12 weeks, 13 to 26 weeks, 27 weeks to end of pregnancy). Concentration – response relationship was analyzed between combined antibody concentration at Day 28 and change from baseline to Day 7 in viral load (VL) in nasopharyngeal (NP) swab sample.

Data & Results: Casirivimab and imdevimab displayed linear PK at the tested doses. Concentrations of antibodies in pregnant patients at end of infusion (EOI) and Day 28 were similar to the adult non-pregnant patients. No significant difference in concentration was observed by trimester of pregnancy at baseline. A slightly lower EOI and higher Day 120 concentration was observed for patients who were in their final trimester at baseline compared to second trimester at baseline. Treatment emergent ADA response against casirivimab and imdevimab were observed in one (1/72) and three (3/72) pregnant patients, respectively. These responses were of low titer ( < 1,000) and had no meaningful effect on concentration of casirivimab and imdevimab in serum. A flat relationship was observed between change from baseline to Day 7 in NP VL and combined mAb concentration in serum at Day 28.

Interpretation, Conclusion or Significance: Casirivimab and imdevimab displayed linear PK and minimal immunogenicity in pregnant outpatients. Similar antibody concentration was observed between pregnant and non-pregnant adult outpatients. Similar response in NP VL reduction was observed in pregnant and non-pregnant patients for all selected doses, which supported the use of 1,200 mg IV dose of REGEN-COV in pregnant outpatients for the treatment of SARS-CoV-2 infection.

Disclosures: All authors in the abstract are current employees/stockholders at Regeneron Pharmaceuticals Inc

Funding: Supported by Regeneron Pharmaceuticals Inc and F. Hoffmann-La Roche Ltd. Certain aspects of this project have been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number: HHSO100201700020C.