Repeat Subcutaneous Administration of REGEN-COV® in Adults is Well-Tolerated and Prevents the Occurrence of COVID-19
RCT 969 patients, 729 treated with monthly subcutaneous casirivimab/imdevimab, showing significantly lower risk of COVID-19 with treatment. There were no grade 3 injection site reactions or hypersensitivity reactions. Slightly more TEAEs were reported with treatment (54.9% vs. 48.3%), due to grade 1-2 ISRs. Serious adverse events were rare and occurred with similar percentages for treatment and control groups. There were no deaths.
NCT04519437 (history).
Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron [Liu, Sheward, Tatham, VanBlargan].
risk of symptomatic case, 92.6% lower, RR 0.07, p = 0.002, treatment 3 of 729 (0.4%), control 13 of 240 (5.4%), NNT 20, odds ratio converted to relative risk.
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risk of case, 92.7% lower, RR 0.07, p = 0.002, treatment 0 of 729 (0.0%), control 10 of 240 (4.2%), NNT 24, odds ratio converted to relative risk, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), seroconversion.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Conflicts of interest:
employee of the drug patent holder.
Isa et al., 16 Nov 2021, Double Blind Randomized Controlled Trial, USA, preprint, 31 authors, trial
NCT04519437 (history).
Contact:
flonza.isa@regeneron.com.
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.11.10.21265889; this version posted November 16, 2021. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .
Repeat Subcutaneous Administration of REGEN-COV® in
Adults is Well-Tolerated and Prevents the Occurrence of
COVID-19
Flonza Isa,1 Eduardo Forleo-Neto,1 Jonathan Meyer,1 Wenjun Zheng,1 Scott
Rasmussen,2 Danielle Armas,3 Masaru Oshita,4 Cynthia Brinson,5 Steven
Folkerth,6 Lori Faria,1 Ingeborg Heirman,1 Neena Sarkar,1 Bret J. Musser,1
Shikha Bansal,1 Meagan P. O’Brien,1 Kenneth C. Turner,1 Samit Ganguly,1
Adnan Mahmood,1 Ajla Dupljak,1 Andrea T. Hooper,1 Jennifer D. Hamilton,1
Yunji Kim,1 Bari Kowal,1 Yuhwen Soo,1 Gregory P. Geba,1 Leah Lipsich,1 Ned
Braunstein,1 George D. Yancopoulos,1 David M. Weinreich,1 Gary A. Herman,1
the COVID-19 Multi-dose Trial Team
1
Regeneron Pharmaceuticals, Inc., Tarrytown, NY; 2Celerion, Lincoln, NE; 3Celerion,
Tempe, AZ; 4Benchmark Research, Sacramento, CA; 5Central Texas Clinical
Research, LLC, Austin, TX; 6Midwest Clinical Research Center, LLC, Dayton, OH.
Correspondence to: Flonza Isa, MD; Email: flonza.isa@regeneron.com
Page 1
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2021.11.10.21265889; this version posted November 16, 2021. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .
Abstract
Background: Data show that a single dose of casirivimab and imdevimab (REGENCOV®) is effective in treating hospitalized individuals and outpatients with COVID-19
and in post-exposure prophylaxis. We present results from a phase 1, double-blind,
placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat
monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers
who were healthy or had chronic stable medical conditions.
Methods: Subjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo
dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints
evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose
administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID19 or SARS-CoV-2 seroconversion.
Results: In total, 969 subjects were treated. Repeat monthly dosing of SC REGENCOV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared
to placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio: 0.07 [95% CI, 0.01–0.27]), and
a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds
ratio 0.00). Development of anti-drug antibodies was low (<5% subjects). No grade
≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. A
slightly higher percentage of subjects reported TEAEs with REGEN-COV (54.9%)
than placebo (48.3%), due to ISRs (all grade 1-2). Serious adverse events were rare
and occurred at similar percentages in the REGEN-COV and placebo groups. No
deaths were reported in the 6-month treatment period.
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medRxiv preprint doi: https://doi.org/10.1101/2021.11.10.21265889; this version..
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