REGN-COV2, an antibody cocktail for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), successfully decreased viral loads in symptomatic patients with coronavirus disease 2019 (COVID-19), according to interim results from a phase 1/2 trial published in the New England Journal of Medicine. The antibody cocktail contained 2 neutralizing antibodies: casirivimab and imdevimab. Results were most striking in patients who were serum antibody-negative or had high viral loads.
Data was collected from 275 non-hospitalized adults with a confirmed SARS-CoV-2 infection. Patients’ median age was 44 years, 49% were men, 13% identified as Black, and 56% identified as Hispanic or Latino. Primary endpoint was the time-weighted average change in viral load from baseline through day 7 in patients who were antibody-negative. Based on recent data linking high viral loads with severe COVID-19, investigators hypothesized that lowering viral loads with REGN-COV2 would improve clinical outcomes, especially in antibody-naïve or high-viral-load patients.
Investigators randomized patients in a 1:1:1 ratio to receive placebo (n=93), low-dose REGN-COV2 (2.4 g; n=88), or high-dose REGN-COV2 (8 g; n=88). Assays for anti-SARS-Cov-2 antibodies were performed on all patients to compare subgroups of antibody-positive versus antibody-negative patients.
Among patients who were serum antibody-negative at baseline, the least-squares mean difference (combined REGN-COV2 dose groups vs placebo group) in the time-weighted average change in viral load was -0.56 log10 copies per milliliter (95% CI, -1.02 to -0.11), and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population.
Patients with the highest viral loads (>107 copies per milliliter) had the largest treatment benefit from REGN-COV2, with a mean viral load reduction 2-log greater than patients who received placebo by day 7. Additionally, most reductions in viral loads were evident by day 3 of the trial.
Both REGN-COV2 dose groups were associated with few and mostly low-grade adverse events. In total, 3% (n=6) of the combined REGN-COV2 groups and 6% (n=6) of the placebo group reported at least one medically attended visit.
The study was limited by the lack of formal hypothesis testing and analyses according to baseline viral load were post hoc.
Based on the interim results, the authors concluded that severe COVID-19 was caused by ongoing viral activity causing prolonged hypoxia and a blunted host immune response, rather than a host’s immune hyper-response.
Additionally, REGN-COV2 serum drug concentrations were well above the predicted neutralization target at day 29 of the study, suggesting that the drug’s long half-life could provide patients with passive immunity for several months.
Disclosure: the trial was designed by Regeneron Pharmaceuticals. Please see the original article for full details on Regeneron’s involvement.
Weinreich DM, Sivapalasingam S, Norton T, et al; for the Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. Published online December 17, 2020. doi:10.1056/NEJMoa2035002