tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2024 May 3;11(6)
fae233.
doi: 10.1093/ofid/ofae233. eCollection 2024 Jun. The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study
Jeff Kingsley[SUP] 1 [/SUP], Nagalingeswaran Kumarasamy[SUP] 2 [/SUP], Luis Abrishamian[SUP] 3 [/SUP], Marc Bonten[SUP] 4 [/SUP], Awawu Igbinadolor[SUP] 5 [/SUP], Martha Mekebeb-Reuter[SUP] 6 [/SUP], Jennifer Rosa[SUP] 7 [/SUP], Damodaran Solai Elango[SUP] 8 [/SUP], Patricia Lopez[SUP] 9 [/SUP], Pierre Fustier[SUP] 10 [/SUP], Susana Goncalves[SUP] 9 [/SUP], Charles G Knutson[SUP] 11 [/SUP], Petra Kukkaro[SUP] 9 [/SUP], Philippe Legenne[SUP] 10 [/SUP], Krishnan Ramanathan[SUP] 9 [/SUP], Shantha Rao[SUP] 12 [/SUP], Evgeniya Reshetnyak[SUP] 12 [/SUP], Vaia Stavropoulou[SUP] 10 [/SUP], Nina Stojcheva[SUP] 10 [/SUP], Michael T Stumpp[SUP] 10 [/SUP], Andreas Tietz[SUP] 9 [/SUP], Marianne Soergel[SUP] 10 [/SUP], Richa Chandra[SUP] 12 [/SUP]
Affiliations
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 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 log[SUB]10[/SUB] 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 log[SUB]10[/SUB] 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.
Keywords: COVID-19; DARPin; SARS-CoV-2; ensovibep; randomized clinical trial.
. 2024 May 3;11(6)
fae233.doi: 10.1093/ofid/ofae233. eCollection 2024 Jun. The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study
Jeff Kingsley[SUP] 1 [/SUP], Nagalingeswaran Kumarasamy[SUP] 2 [/SUP], Luis Abrishamian[SUP] 3 [/SUP], Marc Bonten[SUP] 4 [/SUP], Awawu Igbinadolor[SUP] 5 [/SUP], Martha Mekebeb-Reuter[SUP] 6 [/SUP], Jennifer Rosa[SUP] 7 [/SUP], Damodaran Solai Elango[SUP] 8 [/SUP], Patricia Lopez[SUP] 9 [/SUP], Pierre Fustier[SUP] 10 [/SUP], Susana Goncalves[SUP] 9 [/SUP], Charles G Knutson[SUP] 11 [/SUP], Petra Kukkaro[SUP] 9 [/SUP], Philippe Legenne[SUP] 10 [/SUP], Krishnan Ramanathan[SUP] 9 [/SUP], Shantha Rao[SUP] 12 [/SUP], Evgeniya Reshetnyak[SUP] 12 [/SUP], Vaia Stavropoulou[SUP] 10 [/SUP], Nina Stojcheva[SUP] 10 [/SUP], Michael T Stumpp[SUP] 10 [/SUP], Andreas Tietz[SUP] 9 [/SUP], Marianne Soergel[SUP] 10 [/SUP], Richa Chandra[SUP] 12 [/SUP]
Affiliations
- PMID: 38854392
- PMCID: PMC11160321
- DOI: 10.1093/ofid/ofae233
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 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 log[SUB]10[/SUB] 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 log[SUB]10[/SUB] 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.
Keywords: COVID-19; DARPin; SARS-CoV-2; ensovibep; randomized clinical trial.