Antibody cocktail may help relieve burden from hospitals

Ronapreve, also known as REGEN-COV, appears to reduce the risk of hospitalization or the need for additional treatment among COVID-19 patients when used in a real-world setting, a study has shown. The therapy is seen as a promising way to minimize the impact of SARS-CoV-2 infection on the public healthcare system.

In a cohort of Japanese patients with a confirmed SARS-CoV-2 infection when the delta variant was widely circulating (June 2021 through early September 2021), 13 of 55 patients (23.6 percent) who received antibody cocktail therapy subsequently underwent further medical interventions. In contrast, 22 or 53 patients (41.5 percent) who were initially isolated into nonmedical facilities, where they were under a watch-and-wait situation, were subsequently hospitalized to receive medical interventions. [Int J Infect Dis 2022;doi:10.1016/j.ijid.2022.01.067]

The antibody cocktail therapy lowered the odds for requiring further medical interventions by 70 percent as compared with watchful observation (odds ratio [OR], 0.30, 95 percent confidence interval [CI], 0.10–0.87; p=0.027).

In the ronapreve group, patients with percutaneous oxygen saturation (SpO2) of ≥96 percent showed a favourable response to therapy. At that cutoff, the odds for requiring additional treatment following receipt of the antibody cocktail was lowered by 97 percent (OR, 0.03, 95 percent CI, 0.01–0.22; p<0.001).

The finding on SpO2 may be explained by the suppression of SARS-CoV-2 itself by ronapreve before a surge of inflammation in lungs, according to the investigators.

In addition, the antibody cocktail sped up recovery from COVID-19-related fever by a median of 1 day following administration, “which probably represents an additional benefit for the patients,” they added.

In terms of safety, one patient developed mild swelling of eyelids and urticaria of upper arms during the ronapreve drip, resulting in treatment discontinuation. Also, two patients showed skin eruption around 2–3 hours after the administration.

“Ronapreve is a cocktail made up of two noncompeting neutralizing human IgG1 monoclonal antibodies, casirivimab and imdevimab, that target the receptor-binding domain of the SARS-CoV-2 spike protein, thereby preventing viral entry into human cells through the angiotensin-converting enzyme 2 (ACE2) receptor,” the investigators pointed out. [Science 2020;369:1014-1018; Science 2020;369:1010-1014]

“This cocktail therapy retains neutralization potency against circulating SARS-CoV-2 variants of concern, including B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta) and so forth in vitro and in vivo. However, more recently, some reports have shown that B.1.1.529 (omicron) variant reduced the neutralization by the cocktail antibodies,” they added. [Science 2020;369:1014-1018; Cell 2021;184:3949-3961; Nature 2021;593:130-135]

In the current study, ronapreve was administered at equal doses of 600 mg of casirivimab and imdevimab combined in a 100-ml normal saline solution through intravenous infusion over 30 minutes. Patients who received treatment were under the worse conditions than those in watchful observation in terms of high-risk factors for disease progression.

“Overall, our findings described above are well consistent with data from previous clinical trials regarding ronapreve,” the investigators noted. [N Engl J Med 2021;384:238-251; N Engl J Med 2021;385:1184-1195]