1. Beyond standard of care, ensovibep did not improve outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19) compared to placebo.
2. Although ensovibep was found to be safe, the trial was terminated prematurely due to lack of efficacy.
Level of evidence assessment: 1 (Excellent)
Summary of the study: There are emerging treatments that have been shown to prevent disease progression in early COVID-19, such as oral antiviral agents, intravenous remdesivir, and neutralizing antibodies. Yet therapies for hospitalized patients remain limited. Engineered ankyrin repeat proteins are a new therapeutic approach, designed to bind strongly and specifically to target molecules. Ensovibep is one such class protein, selected to bind to the severe acute respiratory coronavirus-2 (SAR-CoV-2) spike protein and thought to inhibit the virus’s ability to bind and infect cells. Based on positive results from animal studies and human trials in mild to moderate COVID-19, the current phase three randomized controlled trial investigated ensovibep in the treatment of hospitalized patients. Patients were randomized to receive intravenous ensovibep 600 mg or placebo. Overall, there was no significant difference in lung outcomes, sustained recovery, or safety outcomes between ensovibep and placebo. The trial was terminated prematurely due to its futility and ensovibep was found to be ineffective in treating hospitalized patients with COVID-19.
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In depth [randomized control trial]: The current study was a phase three randomized, placebo-controlled trial to investigate the safety and efficacy of ensovibep in the treatment of patients hospitalized with COVID-19. Participants were included if they were 18 years of age or older, hospitalized with PCR-confirmed SARS-CoV-2 infection, and whose COVID-19 symptoms had been present for no more than 12 days at randomization. . A total of 485 patients were randomized 1:1 to receive intravenous ensovibep 600 mg or placebo. Futility was determined based on pulmonary ordinal outcome five days after randomization, characterized by the patient’s need for supportive respiratory therapies, such as supplemental oxygen and noninvasive ventilation. The main measure of effectiveness was sustained recovery at 90 days, defined as the time from randomisation to home discharge for 14 consecutive days. Ordinal lung outcome was assessed for 95% of participants, and sustained recovery at age 90 was recorded for over 96% of participants. The odds ratio (OR) for improved pulmonary outcomes in 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% for ensovibep recipients and 80% for placebo, resulting in a sub-risk ratio [sHR] 1.06 (95% CI, 0.88 to 1.28). The composite safety outcome, which is defined as the incidence rate of adverse events, at day 90 is 32% for ensovibep recipients and 29% for placebo recipients (HR, 1.07; 95% 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.
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