How effective is ensovibep in hospitalized adults with COVID-19?

Hospitalized patients with COVID-19 who are receiving remdesivir and other standard care show no improvements in clinical outcomes with the addition of ensovibep, according to the results of a study.

However, ensovibep is well tolerated, even by seriously ill patients on high-flow nasal oxygen, and results in few hypersensitivity reactions.

“Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection,” the researchers said.

A double-blind, randomized, placebo-controlled, multicentre trial was conducted to determine the efficacy of ensovibep (intravenous, 600 mg), in addition to remdesivir and standard care, among adult patients hospitalized with COVID-19.

The researchers assessed the study drug for early futility based on pulmonary ordinal scores at day 5. Time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge, was the primary outcome. A composite safety outcome included death, serious adverse events, end-organ disease, and serious infections.

After randomly assigning 485 patients to receive an infusion of ensovibep (n=247) or placebo (n=238), enrolment was halted for early futility by an independent data and safety monitoring board. [Ann Intern Med 2022;doi:10.7326/M22-1503]

At day 5, the odds ratio (OR) for a more favourable pulmonary outcome in the ensovibep group was 0.93 (95 percent confidence interval [CI], 0.67‒1.30; p=0.68; an OR >1 would favour ensovibep). The cumulative incidence of sustained recovery at day 90 was 82 percent for ensovibep and 80 percent for placebo (subhazard ratio [sHR], 1.06, 95 percent CI, 0.88‒1.28; an sHR >1 would favour ensovibep).

Finally, the 90-day composite safety outcome was similar between ensovibep and placebo groups (32 percent vs 29 percent; HR, 1.07, 95 percent CI, 0.77‒1.47; an HR <1 would favour ensovibep).

The trial, however, was prematurely stopped due to futility.

“Because enrolment was stopped for futility, the study was underpowered to assess many outcomes, with a wide 95 percent CI for the sHR comparing the primary endpoint of time to sustained recovery across treatment groups,” the researchers said.

The results of this study are comparable to those testing other antiviral agents in the Therapeutics for Inpatients With COVID-19 (TICO) platform. These findings stress the complexity of finding an effective therapy for hospitalized COVID-19 patients receiving background remdesivir, corticosteroids, and other immune modulators, according to the researchers.

For instance, bamlanivimab, sotrovimab, and BRII-196 plus BRII-198 failed the early futility assessment when tested in TICO. This was despite their effectiveness at reducing progression to hospitalization and death in outpatients with early disease. [N Engl J Med 2021;385:1941-1950; N Engl J Med 2021;384:229-237; Lancet Infect Dis 2022;22:622-635; N Engl J Med 2021;384:905-914]

“Overall, a broadly applicable and highly effective antiviral therapy for patients hospitalized with COVID-19 remains a major unmet need,” the researchers said.