Vilobelimab in Combination With Tocilizumab or Baricitinib Dramatically Improves Mortality in Critically Ill COVID-19 Patients: A Subgroup Analysis

A. F. Shorr 1, A. P. J. Vlaar 2, E. H. T. Lim 2, B. P. Burnett 3, C. Chong 4, C. Zink 5, R. Zerbib 6, R. Guo 3, N. Riedemann 6, D. van deBeek 2, C. E. Sandrock 7; 1 MedStar Health and Georgetown University, Washington, DC, United States, 2 Amsterdam UMC,Amsterdam, Netherlands, 3 InflaRx GmbH, InflaRx Pharmaceuticals, Inc., Ann Arbor, MI, United States, 4 lnflaRx GmbH, Munich,Germany, 5 Metronomia Clinical Research GmbH, Munich, Germany, 6 InflaRx GmbH, Munich, Germany, 7 Univ of California AtDavis Med Ctr, Sacramento, CA, United States

https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A5511

Summary

Rationale:

The anti-C5a-specific complement factor blocker, vilobelimab, demonstrated a significant reduction in 28-day all-cause mortality in the PANAMO Phase III global study in adult critically ill COVID-19 patients on top of standard-of-care (SoC) of32% compared to placebo at 42% (HR 0.67, 95%CI:0.48-0.96, p=0.027) (Vlaar et al. 2022). In PANAMO, SoC included use ofcorticosteroids (97%), anti-thrombotic agents (98%) and immunomodulators (20%; tocilizumab> baricitinib). A post-hoc analysiswas performed to evaluate whether any prior or concomitant treatment with immunomodulators provided additional survivalbenefit on top of vilobelimab and SoC.

Methods:

A post-hoc Cox regression subgroup analysis was performed for 28- and 60-Day all-cause mortality in patients with or without prior or concomitant use of tocilizumab or baricitinib when receivingvilobelimab+SoC (Vilo+ or Vilo-) or placebo+SoC (Plc+ or Plc-). In addition, safety was assessed for all groups.

Results:

Seventy-one patients received immunomodulators between the Vilo+ (n=34) and Plc+ (n=37) groups. Demographics of these subgroupswere generally well-balanced and comparable to the overall study. In this post-hoc analysis of the Vilo+ and Plc+ groups, the pointestimate for 28-Day all-cause mortality was 6.3% vs 40.9% (HR 0.13; 95%CI:0.03-0.56, p=0.006). Day 60 all-cause mortality was16.4% vs 49.3% (HR 0.25; 95%CI:0.09-0.68, p=0.006), respectively (Figure 1). Based on these outcomes, the number needed totreat was 2.9 at Day 28 and 3.0 at Day 60. By comparison, the Vilo- (n=143) group had a 28-Day mortality of 37.7% vs 41.7% inthe Plc- group (n=154) (HR 0.81; 95%CI:0.56-1.18, p=0.274), the latter similar to the Plc+ group. Though length of hospital staywas greater in the vilobelimab groups, treatment emergent adverse events (TEAEs) occurred in more than 80% of patients in allgroups. Related TEAEs occurred in a similar proportion of patients in the Vilo+ and Plc+ groups (27.3% vs 21.6%). SeriousTEAEs, however, occurred in fewer patients in the Vilo+ (39.4%) compared to Plc+ (70.3%) which was comparable to Vilo-(63.4%) and Plc- (61.8%) groups. Unspecified and bacterial infections were observed in fewer Vilo+ patients compared to Plc+patients, while viral and fungal infections were comparable. Conclusion: In addition to corticosteroid and anti-thrombotic agentadministration, this post-hoc analysis with a small number of patients suggests that the co-administration of vilobelimab withbaricitinib or tocilizumab may have further potential to improve survival in critically ill COVID-19 patients.

This abstract is funded by: InflaRx N.V.