Antibody Cocktail Helps Reduce COVID-19 Virus Levels in Outpatient Setting

Regeneron’s investigational antibody cocktail, REGN-COV2, significantly reduced virus levels and need for further medical visits in patients with coronavirus disease 2019 (COVID-19), according to results from a phase 2/3 trial.

REGN-COV2, a combination of monoclonal antibodies REGN10933 and REGN10987, was designed specifically to block infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the ongoing phase 2/3 seamless trial in the COVID-19 outpatient setting, REGN-COV2 met the primary and key secondary end points, according to the findings. The randomized, double-blind trial is evaluating the effect of adding REGN-COV2 to usual standard of care, compared with adding placebo to standard-of-care.

The latest data from the trial include an analysis of 523 patients, in addition to data from the first 275 patients which was previously reported.

According to the results, the most recent analysis demonstrated that the trial met all of the first 9 end points in the statistical hierarchy, which assessed virologic end points based on viral load, seronegative status and dose group, as well as the key clinical end point of COVID-19 related medically-attended visits.

The virologic results showed:

• The average daily change in viral load through day 7 in patients with high viral load was a 0.68 log10 copies/mL greater reduction with REGN-COV2 compared with placebo (combined dose groups; p<0.0001). There was a 1.08 log greater reduction with REGN-COV2 treatment by day 5, which corresponds to REGN-COV2 patients having, on average, a greater than 10-fold reduction in viral load, compared with placebo.
• In the overall patient group with detectable virus at baseline, the average daily reduction in viral load through day 7 was a 0.36 log10 copies/mL greater reduction with REGN-COV2, compared with placebo (combined dose groups; p=0.0003).
• Patients with a higher viral load at baseline and/or no detectable antibodies at baseline (suggesting their bodies had not yet mounted an effective immune response), derived greater benefit from REGN-COV2 therapy.

The clinical results in the overall population:

1. Treatment with REGN-COV2 reduced COVID-19 related medical visits by 57% through day 29 (2.8% combined dose groups; 6.5% placebo; p=0.024).
2. Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with 1 or more risk factor (combined dose groups; nominal p=0.0065).

Investigators noted that the results showed no significant difference in virologic or clinical efficacy between the REGN-COV2 high dose (8 grams) and low dose (2.4 grams). Regeneron said that it is reviewing potential changes to dosing in the ongoing outpatient trial given the current limited supply of the drug.

REGN-COV2 was generally well tolerated in the trial, with more frequent severe adverse events (AEs) in patients treated with REGN-COV2 versus placebo. More infusion reactions occurred with the high-dose REGN-COV2 compared with placebo (1.5% high dose, 0% low dose, 0.4% placebo).

“We continue to see the strongest effects in patients who are most at risk for poor outcomes due to high viral load, ineffective antibody immune response at baseline, or pre-existing risk factors,” George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, said in a statement.

According to Yancopolous, Regeneron has shared the results with the FDA as part of its review of REGN-COV2’s emergency use authorization (EUA) submission and plans to submit detailed results of the trial for publication.

Reference:

1. Regeneron’s COVID-19 Outpatient Trial Prospectively Demonstrates That REGN-COV2 Antibody Cocktail Significantly Reduced Virus Levels and Need for Further Medical Attention. News release. Regeneron; October 28, 2020. Accessed October 30, 2020. https://investor.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates​