Another Monoclonal Antibody Combo Cuts Risk of Severe COVID Outcomes

A combination monoclonal antibody therapy significantly reduced hospitalization and death versus placebo in COVID-19 patients at high risk of progressing to severe disease, according to interim data from the phase III ACTIV-2 platform trial, which was shared by manufacturer Brii Biosciences on Tuesday.

In over randomized 800 patients, the combination of BRII-196/BRII-198 reduced the risk of a composite endpoint of hospitalization and death by 78% (relative risk 0.22, 95% CI 0.05-0.86, P<0.00001).

Partial follow-up found fewer overall hospitalizations in the intervention arm (12 vs 45 in controls) as well as deaths (one vs nine, respectively).

A lower percentage of the intervention group experienced grade 3 or higher adverse events compared with placebo (3.8% vs 13.4%), and “few” events were thought to be drug-related, Brii Biosciences noted. There were no serious adverse events or deaths in the trial.

After evaluating 69% of enrolled patients through the primary endpoint — hospitalization and death within 28 days following the treatment — as part of a prespecified review, the combination demonstrated statistical significance. An independent data safety and monitoring board recommended the release of the results while follow-up is ongoing, the company added.

“We expect that the final study results will solidify this combination monoclonal antibody treatment as a new COVID-19 therapeutic option,” said co-lead investigator Eric S. Daar, MD, of the Lundquist Institute at Harbor-UCLA Medical Center in Torrance, California, in a statement.

The BRII-196/BRII-198 arm of the ACTIV-2 platform trial, which is sponsored by the National Institute of Allergy and Infectious Diseases, enrolled 837 outpatients with COVID-19 who were at risk of progression to severe disease due to age (older than age 60) or with pre-existing medical conditions at any age. They were enrolled within 10 days of symptom onset.

Trial follow-up is ongoing, and Brii Biosciences noted that additional subgroup analyses are examining the clinical benefit of early treatment (less than 5 days) compared with late treatment (6-10 days).

The antibody combination showed efficacy against SARS-CoV-2 variants, including Alpha (B.1.1.7), Delta (B.1.617.2), and Lambda (C.37) during in vitro studies, they said.

Results of the entire ACTIV-2 trial — which includes patients treated from January to July 2021 in the U.S., Brazil, South Africa, Mexico, Argentina, and the Philippines — will include an analysis of BRII-196/BRII-198 by variant type.

Last Updated August 25, 2021