(645) Vilobelimab With Baseline Vasopressor Use Improves Mortality in Critically Ill COVID-19 Patients

Introduction: Vasopressors in septic shock patients are used to restore and maintain blood pressure. But in critically ill COVID-19 patients, vasopressor use is associated with significantly higher in-hospital and 30-day mortality as assessed by a large meta-analysis of observational studies (Mermiri et al. 2023). The anti-C5a complement blocker, vilobelimab, significantly reduced 28-day all-cause mortality (32% vs 42%; HR 0.67, 95% CI: 0.48 - 0.96, p=0.027) in critically ill, septic and moderate-to-severe ARDS COVID-19 patients (PANAMO, N=368: NCT04333420; Vlaar et al. 2022). Because most patients enrolled in PANAMO were on vasopressor therapy when administered vilobelimab, we sought to assess the effect on mortality compared to placebo in critically ill COVID-19 patients.

Methods: An age-adjusted Cox regression analysis was performed to determine 28-day all-cause mortality with and without baseline vasopressor use in the vilobelimab (n=177) and placebo (n=191) groups (Full Analysis Set).

Results: In PANAMO, 115 (65.0%) and 138 (72.2%) critically ill COVID-19 patients were on vasopressors at baseline in the vilobelimab and placebo arms, respectively. During the 28-Day period analyzed, 160 (90.4%) and 190 (99.5%) patients received vasopressors in the vilobelimab and placebo arms, respectively, with norepinephrine the most commonly administered agent in both groups. In patients receiving baseline vasopressors, Kaplan Meier estimates of mortality at 28-Days in the vilobelimab arm was 32.2% (95% CI: 24.4% - 41.7%) compared to 43.1% (95% CI: 35.2% -52.0%) for placebo (HR 0.63; 95% CI: 0.41 - 0.96, p=0.0298). In patients with no baseline vasopressor use, Kaplan Meier estimates of mortality at 28-Days in the vilobelimab arm (n=62, 35.0%) was 30.4% (95% CI: 20.4% - 43.9%) compared to 37.7% (95% CI: 26.2% - 52.2%) for placebo (n=55, 28.8%) (HR 0.80; 95% CI: 0.42 - 1.51, p=0.4829).

Conclusions: Treatment with vilobelimab with baseline vasopressor use led to significantly improved survival compared to placebo with baseline vasopressors in critically ill COVID-19 patients. These results warrant further study of vilobelimab in septic patients with baseline vasopressor use.