Antibody cocktail cuts hospitalization, death in COVID-19
The REGN-COV2 monoclonal antibody cocktail comprising casirivimab and imdevimab significantly reduces the risk of hospitalization and all-cause death by 71 percent compared with placebo in nonhospitalized patients with COVID-19, according to a large phase III study presented at the ATS 2021 Meeting.
“As high SARS-CoV-2 viral load has been associated with increased disease severity and higher mortality, treatments that reduce viral burden may improve COVID-19 clinical outcomes,” said presenting author Dr Julie Philley from the University of Texas Health Science Center in Tyler, Texas, US.
“Monoclonal antibody-based treatments that neutralize SARS-CoV-2 appear to be an effective treatment modality,” she pointed out.
The combination of casirivimab and imdevimab contains two potent, neutralizing antibodies which target distinct noncompeting epitopes on the receptor binding domain of the SARS-CoV-2 spike protein, explained Philley.
In this phase III trial, 4,567 outpatients diagnosed with COVID-19 were randomized 1:1:1 to receive a single dose of intravenous casirivimab with imdevimab 2,400 mg or 1,200 mg or placebo and followed through 29 days. [ATS 2021, session B007]
The primary endpoint of hospitalization due to COVID-19 or all-cause mortality was significantly reduced by 71 percent in patients treated with the antibody cocktail, regardless of whether it was high dose (hazard ratio [HR], 0.29; p<0.0001) or low dose (HR, 0.29; p=0.0014), compared with placebo.
“The difference between the treatment and placebo groups was seen as early as day 4 and sustained through day 29,” noted Philley.
Also, the clinical benefits with antibody cocktail therapy were consistent across subgroups, regardless of baseline viral load and seropositive/negative status.
In addition, patients treated with the antibody cocktail saw their symptoms resolved 4 days earlier on average compared with those on placebo (median symptom duration, 10 vs 14 days).
Consistent with results of earlier phase studies, both doses of the antibody cocktail led to substantial reduction in viral load from baseline, and by magnitudes that were greater than those seen with placebo.
“The antibody cocktail has acceptable and well tolerated safety profile, with no new serious safety concerns identified,” stated Philley.
Serious adverse events (AEs) and AEs of special interest (AESIs) occurred more commonly in the placebo group than the antibody cocktail group. “Very few patients experienced AESIs of infusion-related reactions and hypersensitivity reactions in the antibody cocktail group,” she reported.
When asked about the theoretical risk of viral mutations, Philley said the antibody cocktail still retained certain neutralization activity against variants of concern such as those originating from Brazil and California.
“The use of both casirivimab and imdevimab in combination reduces the risk of emergence of treatment-resistant variants [compared with single antibody alone],” she added.