The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study
Kingsley, Jeff; Kumarasamy, Nagalingeswaran; Abrishamian, Luis; Bonten, Marc; Igbinadolor, Awawu; Mekebeb-Reuter, Martha; Rosa, Jennifer; Solai Elango, Damodaran; Lopez, Patricia; Fustier, Pierre; Goncalves, Susana; Knutson, Charles G; Kukkaro, Petra; Legenne, Philippe; Ramanathan, Krishnan; Rao, Shantha; Reshetnyak, Evgeniya; Stavropoulou, Vaia; Stojcheva, Nina; Stumpp, Michael T; Tietz, Andreas; Soergel, Marianne; Chandra, Richa
(2024) Open Forum Infectious Diseases, volume 11, issue 6
(Article)
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic was characterized by rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, affecting viral transmissibility, virulence, and response to vaccines/therapeutics. EMPATHY (NCT04828161), a phase 2 study, investigated the safety/efficacy of ensovibep, a multispecific designed ankyrin repeat protein (DARPin) with multivariant in
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vitro activity, in ambulatory patients with mild to moderate COVID-19. Methods: Nonhospitalized, symptomatic patients (N = 407) with COVID-19 were randomized to receive single-dose intravenous ensovibep (75, 225, or 600 mg) or placebo and followed until day 91. The primary endpoint was time-weighted change from baseline in log10 SARS-CoV-2 viral load through day 8. Secondary endpoints included proportion of patients with COVID-19-related hospitalizations, emergency room (ER) visits, and/or all-cause mortality to day 29; time to sustained clinical recovery to day 29; and safety to day 91. Results: Ensovibep showed superiority versus placebo in reducing log10 SARS-CoV-2 viral load; treatment differences versus placebo in time-weighted change from baseline were -0.42 (P =. 002), -0.33 (P =. 014), and -0.59 (P <. 001) for 75, 225, and 600 mg, respectively. Ensovibep-treated patients had fewer COVID-19-related hospitalizations, ER visits, and all-cause mortality (relative risk reduction: 78% [95% confidence interval, 16%-95%]) and a shorter median time to sustained clinical recovery than placebo. Treatment-emergent adverse events occurred in 44.3% versus 54.0% of patients in the ensovibep and placebo arms; grade 3 events were consistent with COVID-19 morbidity. Two deaths were reported with placebo and none with ensovibep. Conclusions: All 3 doses of ensovibep showed antiviral efficacy and clinical benefits versus placebo and an acceptable safety profile in nonhospitalized patients with COVID-19.
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Keywords: COVID-19, DARPin, SARS-CoV-2, ensovibep, randomized clinical trial, Infectious Diseases, Oncology
ISSN: 2328-8957
Publisher: Oxford University Press
Note: Publisher Copyright: © 2024 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
(Peer reviewed)