Phase III findings from Regeneron Pharmaceuticals’ trial of its combination monoclonal antibody treatment REGEN-COV show the therapy to be associated with significant reductions in Covid-19-related hospitalization and death at half the dose originally recommended by the FDA.
Compared to placebo, treatment with REGEN-COV was also associated with faster resolution of symptoms and reduced SARS-CoV-2 viral load.
The casirivimab-imdevimab combination treatment was granted an emergency use authorization (EUA) by the FDA last November at a dosage of 2,400-mg for patients with mild to moderate Covid-19 at risk for progression to severe disease.
The phase III trial data showed little difference in key trial outcomes among patients receiving this dosage and those receiving 1,200-mg of the monoclonal antibody cocktail.
Last June, the FDA approved a reduced dose of REGEN-COV to be given by subcutaneous injection in settings where intravenous infusions are not possible in an effort to increase access to the treatment. Late this summer, the FDA expanded the EUA to include prophylactic treatment of people without Covid-19 at high risk for hospitalization or death who have been exposed to SARS-CoV-2.
This week the World Health Organization (WHO) also signed off on the use of the monoclonal antibody cocktail for the treatment of Covid-19 patients at increased risk for severe disease, and the health organization also called for more equitable global access to the therapy.
REGEN-COV was developed as a treatment for Covid-19 that would remain active against emerging variants of the disease, wrote trial researchers David Weinreich, MD, of Regeneron Pharmaceuticals, and colleagues, in The New England Journal of Medicine.
High-throughput screening was used “to generate an antibody cocktail consisting of two SARS-CoV-2 neutralizing antibodies against distinct, non-overlapping epitopes on the spike protein,” the study authors wrote.
Phase I-II data from the Regeneron Pharmaceuticals sponsored REGEN-COV trial confirmed activity against Covid-19 and the phase III phase of the adaptive trial involved outpatients with Covid-19 who had risk factors for progression to severe disease. The patients were treated with various doses of REGEN-COV or placebo and followed through day 29.
Based on phase I-II data, which showed similar efficacy for 8,000-mg and 2,400 mg doses, the phase III trial included doses of 2,400 mg (1,200 each of casirivimab and imdevimab) or 1,200-mg (600 mg of each antibody).
Among patients treated with REGEN-COV 2,400-mg, 1.3% experienced Covid-19-related hospitalization or death, compared to 4.6% of those in the matching placebo group, for a relative risk reduction of 71.3% (P<0.001).
Among patients treated with REGEN-COV 1,200-mg, 1.0% experienced Covid-19-related hospitalization or death, compared to 3.2% of those in the matching placebo group, for a relative risk reduction of 70.4% (P=0.002).
Compared to placebo, both REG-COV doses were associated with a 4 day shorter time to resolution of systems (10 days versus 14 days; P<0.001 for both doses).
REGEN-COV was found to be effective in all subgroups included in the study, including patients who were antibody-positive at baseline.
“Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was −0.71 log10 copies per milliliter (95% CI, −0.90 to −0.53) in the 1200-mg group and −0.86 log10 copies per milliliter (95% CI, −1.00 to −0.72) in the 2400-mg group,” the researchers wrote.
Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%) and infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.
“Previous data from the phase I-II portion of this trial showed that in outpatients with Covid-19, REGEN-COV lowered the viral load, reduced the need for medical attention related to Covid-19, and may have reduced the risk of hospitalization,” Weinreich and colleagues wrote.
“The phase III clinical outcomes data presented here are consistent with and strengthen these findings showing that early use of REGEN-COV in outpatients with risk factors for severe Covid-19 can lower the risk of hospitalization or death from any cause.”
They concluded that the phase 3 data “showed that the 1,200-mg dose of REGEN-COV, like the 2,400-mg dose, reduced the risk of Covid-19-related hospitalization or death and sped the time to recovery.”
Phase 3 findings from a key REGEN-COV trial show the therapy to be associated with significant reductions Covid-19-related hospitalization and death at both 2,400-mg and 1,200-mg doses.
The phase III data showed little difference in key trial outcomes among patients receiving 1,200-mg and 2,400-mg of the monoclonal antibody cocktail.
Salynn Boyles, Contributing Writer, BreakingMED™
This trial was funded by Regeneron Pharmaceuticals and others (Clinical-Trials.gov number, NCT04425629). David Weinreich and other researchers are employees of Regeneron.
Cat ID: 926
Topic ID: 79,926,933,926,927,928,934