Vilobelimab treatment effect on 28-day all-cause mortality in severe ards covid-19 patients in panamo: a phase 3 rct

SESSION TITLE: Blood and Drugs in the ICU SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: The C5a-specific monoclonal antibody, vilobelimab (Vilo), significantly reduced 28-day all-cause mortality in invasively mechanically ventilated, critically ill COVID-19 patients in the international phase 3, randomized, double-blind, placebo (Plc)-controlled PANAMO study (Vlaar APJ, et al. 2022). In a prespecified subgroup of severe acute respiratory distress syndrome (ARDS) COVID-19 patients (PaO2/FiO2≤100 mmHg), 28-day all-cause mortality was also significantly reduced. Additional post-hoc mortality analysis of COVID-19-induced ARDS patients was performed by prespecified region (Western Europe, South America, Russia/South Africa) to evaluate potential differences. METHODS: COVID-19 patients (N=368) enrolled within 48 hours of intubation received up to six, 800mg infusions of Vilo (n=177) or Plc (n=191) on top of standard-of-care. Analysis of 28-day all-cause mortality was performed for all patients and by region in severe ARDS COVID-19 patients using Cox regression. RESULTS: Mean age (Vilo 56.7 years, Plc 55.9 years), sex (male: Vilo 71%, Plc 66%) and proportion of severe ARDS patients at baseline (PaO2/FiO2≤100 mmHg) (Vilo n=43, 24.3% vs Plc n=55, 28.8%) were comparable between groups in the study. Overall, Vilo statistically reduced all-cause 28-day mortality in severe ARDS patients (Vilo 40% vs Plc 59.5%: HR 0.55; 95% CI:0.30-0.98, P=0.044). Severe ARDS patient mean age differed per region with Western Europe having an older population (Vilo 60.9±11.7 years, Plc 65.0±11.2 years) compared to South America (Vilo 47.1±10.7 years, Plc 47±14.7 years) and Russia/South Africa (Vilo 52.9±14.1 years, Plc 58.1±13.0 years). Males were predominant in each region: Western Europe (Vilo 70.8%, Plc 66.7%); South America (Vilo 81.2%, Plc 60%); and Russia/South Africa (Vilo 62.5%, Plc 50%). Severe ARDS patients in Western Europe (Vilo n=24, Plc n= 27) had a 20.8% mortality with Vilo vs 51.9% for Plc, a 60% relative reduction in mortality (HR 0.37; 95%CI: 0.13-1.05). South America (Vilo n=11, Plc n=20) had a 68.8% mortality with Vilo vs 56% Plc (HR 1.03; 95%CI: 0.40-2.70), and Russia/South Africa (Vilo n=8, Plc n=8) a 68% mortality with Vilo vs 100% Plc (HR 0.37; 95%CI: 0.11-1.22). Similar mortality was sustained out to day 60 in each region. CONCLUSIONS: Severe ARDS COVID-19 patients benefited from Vilo worldwide and especially in Western Europe. A confirmative study in severe ARDS in the context of COVID-19 or another respiratory disease is needed to determine the efficacy in these critically ill patients. CLINICAL IMPLICATIONS: Vilobelimab represents a new therapy which may effectively treat COVID-19-induced severe ARDS. DISCLOSURES: Advisory Committee Member relationship with Alexion Please note: March 20 ongoing Added 03/31/2023 by Djillali Annane, source=Web Response, value=Honoraria No relevant relationships by Michael Bauer No relevant relationships by Alexander Cornet No relevant relationships by LUIS HERCILLA VASQUEZ No relevant relationships by Philippe Jorens No relevant relationships by Jose Francisco Kerr Saraiva Speaker/Speaker's Bureau relationship with InflaRx Please note: 21-25 Mar 2023 Added 04/03/2023 by Endry Lim, source=Web Response, value=Registration, travel, stay Removed 04/03/2023 by Endry Lim, source=Web Response Speaker/Speaker's Bureau relationship with InflaRx Please note: 21-25 Mar 2023 Added 04/03/2023 by Endry Lim, source=Web Response, value=Conference costs, travel, stay No relevant relationships by Suzana Margareth Lobo No relevant relationships by Gernot Marx Paid investigator relationship with InflaRx Please note: 2021-2022 Added 04/06/2023 by Bruno Mourvillier, source=Web Response, value=Honoraria Presenting author relationship with InflaRX Please note: 2022-2023 Added 04/06/2023 by Bruno Mourvillier, source=Web Response, value=Travel No relevant relationships by Pieter Tuinman No relevant relationships by Pieter van Paassen No relevant relationships by Martin Witzenrath