1. Beyond standard care, ensovibep did not improve outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients compared to placebo.

2. Although ensovibep was found to be safe, the trial was stopped early due to lack of efficacy.

Evidence Rating Level: 1 (Excellent)

Study Rundown: There are emergenging treatments that have proven effective in preventing disease progression in early COVID-19, such as oral antiviral agents, intravenous remdesivir, and neutralizing antibodies. Yet, therapies for hospitalized patients remain limited. Designed ankyrin repeat proteins are a new approach to therapeutics, engineered to bind strongly and specifically to target molecules. Ensovibep is a protein of this class, selected to bind to the severe acute respiratory coronavirus-2 (SAR-CoV-2) spike protein and purported to inhibit the virus’s ability to bind and infect cells. Based on positive results in animal studies and human trials of mild to moderate COVID-19, the current phase three randomized controlled trial investigated ensovibep in treating hospitalized patients. Patients were randomized to receive intravenous ensovibep at 600mg or a placebo. Overall, there was no significant difference in pulmonary outcomes, sustained recovery, or safety outcomes between ensovibep and placebo. The trial was stopped early due to futility and ensovibep was found to be inefficacious in the treatment of hospitalized COVID-19 patients.

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In-Depth [randomized control trial]: The current study was a phase three randomized, placebo-controlled trial to study the safety and efficacy ensovibep in the treatment of patients hospitalized with COVID-19. Participants were included if they were 18 years of age or older, hospitalized with a SARS-CoV-2 infection as confirmed by PCR, and whose COVID-19 symptoms had been present for at most 12 days at randomization. Overall 485 patients were randomized 1:1 to receive intravenous ensovibep at 600mg or placebo. Futility was determined based on ordinal pulmonary outcome five days after randomization, as characterized by the patient’s need for supportive respiratory therapies, such as supplemental oxygen and noninvasive ventilation. The primary efficacy outcome was sustained recovery at 90 days, defined as time from randomization to home discharge for 14 consecutive days. The ordinal pulmonary outcome was assessed for 95% of participants, and sustained recovery at 90 was recorded for more than 96% of participants. The odds ratio (OR) for an improvement in pulmonary outcome in the ensovibep recipients (compared to placebo) was 0.93 (95% confidence interval [CI], 0.67 to 1.30, p=0.68). Similarly, the sustained recovery rate was 82% among ensovibep recipients and 80% for placebo, resulting in a subhazard ratio [sHR] of 1.06 (95% CI, 0.88 to 1.28). Composite safety outcome, which is defined as adverse event incidence rate, at day 90 is 32% for ensovibep recipients and 29% for placebo recipients (HR, 1.07; 95% CI 0.77 to 1.47). Mortality rates were also comparable between the two groups (HR, 0.83; 95% CI 0.51 to 1.35). Despite its safety, these results showed that ensovibep did not improve clinical outcomes beyond standard care in patients hospitalized with COVID-19 and did not support its use in this patient population.

Image: PD

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