ABSTRACT
Background: Ensovibep is a multi-specific DARPin (designed ankyrin repeat protein) therapeutic in clinical development for treatment of COVID-19. In Part A (Phase 2) of the EMPATHY study, ensovibep treatment demonstrated greater viral load decline versus placebo (Pbo), and a relative risk reduction for hospitalization, ER visits and death. We report the sustained clinical recovery data from Phase 2 of EMPATHY. Method(s): Patients (pts) were eligible for EMPATHY (NCT04828161) when presenting >=2 mild-to-moderate COVID19 symptoms (onset within 7 days) and a positive SARS-CoV-2 rapid antigen test on day of dosing. 407 pts were randomised (1:1:1:1) to ensovibep (600, 225 or 75mg) or Pbo as single, IV infusion. The FDA COVID-19 symptom questionnaire was used (daily to Day 15, and on Days 22, 29) to assess time to sustained clinical recovery (secondary endpoint). Result(s): Ensovibep treatment was associated with a shorter time to sustained clinical recovery versus Pbo (Fig 1). The median time to sustained recovery were 23 days, 15 days, 14 days, and 29 days in 600mg, 225mg, 75mg, placebo arms, respectively. The cumulative proportion of patients with sustained clinical recovery by Day 15 were 44%, 54%, 55% and 36% in 600mg, 225mg, 75mg, and placebo arms, respectively. Conclusion(s): Ensovibep administration was associated with earlier sustained clinical recovery versus placebo.
ABSTRACT
Background. Ensovibep is a multi-specific DARPin (designed ankyrin repeat protein) antiviral in clinical development for treatment of COVID-19. In the Phase 2 EMPATHY study, ensovibep demonstrated greater viral load decline versus placebo. Here we report (1) the efficacy of ensovibep in patients with and without anti-SARS-CoV-2 antibodies at baseline and (2) SARS-CoV-2 mutation emergence data with treatment. Methods. Eligible ambulatory patients with >=2 COVID-19 symptoms (onset within 7 days) and positive SARS-CoV-2 rapid antigen test on day of dosing, were randomized (1:1:1:1) to ensovibep (600, 225 or 75 mg) or placebo as single, IV infusion. Chemiluminescent immunoassays were used for antibody detection (SARS-CoV-2 S1/S2 IgG and SARS-CoV-2 IgM). A pre-specified subgroup analysis was performed based on baseline anti-SARS-CoV-2 antibody status. Analysis of changes in viral genome from baseline to post baseline was performed to evaluate treatment-emergent mutations. Results. Of the patients analyzed, 48.5% had anti-SARS-CoV-2 antibodies at baseline. Baseline log10 SARS-CoV-2 viral load (mean +/-SD) was similar across groups [ensovibep (all doses) 6.5 +/-1.5, placebo 6.2 +/-1.5];> 90% were infected with the Delta (B.1.617.2) variant. SARS-CoV-2 viral load reduction up to Day 8 showed similar effects in favor of ensovibep compared with placebo regardless of the presence of anti-SARS-CoV-2 antibodies (Figure 1). Patients in ensovibep 75 mg, 600 mg, and placebo groups had comparable incidences of emergent mutations, with a higher incidence in the 225 mg group. Based on analysis of 70% of the expected viral sequencing data, two mutations in the key binding residues of ensovibep were observed (Y489H and F486L) in a total of three patients treated with ensovibep. These patients either cleared virus by Day 8 or mutations were transient (occurred at a single time point but not later in the course of infection). (Figure Presented) Conclusion. Ensovibep effectively reduces SARS-CoV-2 viral load regardless of the presence of anti-SARS-CoV-2 antibodies at baseline. Furthermore, there were no emerging mutations of concern, indicating that a single dose administration of ensovibep is associated with minimal selective pressure.