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All Studies   Meta Analysis    Recent:   

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 et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae233, EMPATHY, NCT04828161
May 2024  
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Mortality 89% Improvement Relative Risk Hospitalization/ER 78% Hospitalization 87% ER visit 87% Recovery, 600mg 30% Recovery, 225mg 39% Recovery, 75mg 39% PASC -1% Ensovibep  EMPATHY  EARLY TREATMENT  DB RCT Is early treatment with ensovibep beneficial for COVID-19? Double-blind RCT 400 patients in multiple countries (May - Oct 2021) Fewer hosp./ER visits (p=0.017) and lower hospitalization (p=0.012) c19early.org Kingsley et al., Open Forum Infectious.., May 2024 Favorsensovibep Favorscontrol 0 0.5 1 1.5 2+
RCT 407 mild to moderate COVID-19 outpatients showing faster viral clearance, lower risk of hospitalization/ER visits, and shorter time to sustained recovery with ensovibep treatment (75/225/600mg single infusion). There were 2 COVID-19 related deaths in the placebo group and none in the ensovibep groups.
risk of death, 89.0% lower, RR 0.11, p = 0.06, treatment 0 of 301 (0.0%), control 2 of 99 (2.0%), NNT 49, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of hospitalization/ER, 78.1% lower, RR 0.22, p = 0.02, treatment 4 of 301 (1.3%), control 6 of 99 (6.1%), NNT 21.
risk of hospitalization, 86.8% lower, RR 0.13, p = 0.01, treatment 2 of 301 (0.7%), control 5 of 99 (5.1%), NNT 23.
ER visit, 86.8% lower, RR 0.13, p = 0.01, treatment 2 of 301 (0.7%), control 5 of 99 (5.1%), NNT 23.
risk of no recovery, 29.6% lower, HR 0.70, p = 0.13, treatment 100, control 99, inverted to make HR<1 favor treatment, Cox proportional hazards, 600mg.
risk of no recovery, 39.4% lower, HR 0.61, p = 0.03, treatment 100, control 99, inverted to make HR<1 favor treatment, Cox proportional hazards, 225mg.
risk of no recovery, 39.4% lower, HR 0.61, p = 0.03, treatment 101, control 99, inverted to make HR<1 favor treatment, Cox proportional hazards, 75mg.
risk of PASC, 0.9% higher, RR 1.01, p = 1.00, treatment 146 of 243 (60.1%), control 50 of 84 (59.5%), day 91.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Kingsley et al., 3 May 2024, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 23 authors, study period 10 May, 2021 - 21 October, 2021, trial NCT04828161 (history) (EMPATHY). Contact: richa.chandra@novartis.com, andreas.tietz@novartis.com.
This PaperEnsovibepAll
The darpin antiviral ensovibep for non-hospitalized patients with COVID-19: Results from EMPATHY, a randomized, placebo-controlled Phase 2 study
Jeff Kingsley, Nagalingeswaran Kumarasamy, Luis Abrishamian, Marc Bonten, Awawu Igbinadolor, Martha Mekebeb-Reuter, Jennifer Rosa, Damodaran Solai Elango, Patricia Lopez, Pierre Fustier, Susana Goncalves, Charles G Knutson, Petra Kukkaro, Philippe Legenne, Krishnan Ramanathan, Shantha Rao, Evgeniya Reshetnyak, Vaia Stavropoulou, Nina Stojcheva, Michael T Stumpp, Andreas Tietz, Marianne Soergel, Richa Chandra
doi:10.1093/ofid/ofae2331
pandemic was characterized by rapid evolution of SARS-CoV-2 variants, affecting viral transmissibility, virulence, and response to vaccines/therapeutics.
Conflict of interest Dr Kingsley reports receiving grants or contracts from Pfizer, Regeneron, Lilly, Novavax, Boehringer Ingelheim, GlaxoSmithKline, Merck, Clear Creek, National Institute of Allergy and Infectious Disease, and Azur; Dr Kumarasamy reports receiving grants or contracts from Hetero Labs, Viatris, Emcure, Johnson & Johnson, NIH, ICMR, and WHO; Dr Abrishamian reports payment for expert testimony by individual law firms and insurance companies; Dr Bonten reports receiving grants or contracts from Janssen Vaccines, Novartis, and CureVac; consulting fees from AstraZeneca, Pfizer, Janssen Vaccines and Novartis; participation on a Data Safety Monitoring Board or Advisory Board for Sanofi (all payments to UMC Utrecht); and honoraria for lectures by Takeda; and participation in a Data Safety Monitoring Board or Advisory Board for Sanofi; Dr Igbinadolor, Dr Mekebeb-Reuter and Dr Rosa report no conflicts of interests; Reshetnyak is an employee of Novartis; Dr Chandra, Dr Solai Elango, Ms Goncalves, Dr Kukkaro, Dr Lopez, Dr Tietz, Dr Knutson, and Dr Rao are employees at Novartis and hold stock or stock options in the company; Dr Legenne, Dr Stavropoulou, Dr Soergel and Dr Stojcheva are employees at Molecular Partners AG and hold stock or stock options in the company; Dr Stumpp is an employee at Molecular Partners AG, a member of its executive management and owns shares in the company. At the time of writing this manuscript, Dr Fustier was an employee at Molecular..
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EMPATHY (NCT04828161), a Phase 2 study, investigated the ' 'safety/efficacy of ensovibep, a multi-specific designed ankyrin repeat protein (DARPin) with ' 'multi-variant in vitro activity, in ambulatory patients with mild-to-moderate ' 'COVID-19.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>Non-hospitalized, symptomatic patients (N\u2009=\u2009407) with ' 'COVID-19 were randomized to receive single-dose intravenous ensovibep (75, 225, or 600\u2005' '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.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>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\u2009=\u20090.002), –0.33 (p\u2009=\u20090.014), and –0.59 (p\u2009' '&amp;lt;\u20090.001) for 75, 225, and 600\u2005mg, respectively. Ensovibep-treated patients ' 'had fewer COVID-19-related hospitalizations, ER visits, and all-cause mortality (relative ' 'risk reduction: 78%; 95% CI: 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.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>All 3 doses of ensovibep showed antiviral efficacy and clinical ' 'benefits versus placebo and an acceptable safety profile in non-hospitalized patients with ' 'COVID-19 (Funded by Novartis).</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/ofid/ofae233', 'type': 'journal-article', 'created': {'date-parts': [[2024, 5, 3]], 'date-time': '2024-05-03T20:07:25Z', 'timestamp': 1714766845000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The DARPin antiviral ensovibep for non-hospitalized patients with COVID-19: Results from ' 'EMPATHY, a randomized, placebo-controlled Phase 2 study', 'prefix': '10.1093', 'author': [ { 'given': 'Jeff', 'family': 'Kingsley', 'sequence': 'first', 'affiliation': [{'name': 'IACT Health DBA Centricity Research , Columbus, GA , USA'}]}, { 'given': 'Nagalingeswaran', 'family': 'Kumarasamy', 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