Inhibition of Relevant Clinical and Pathway Biomarkers in Patients with COVID-19 Pneumonia and Inflammation in a Phase 2 Multicenter Randomized Study with MAS825, an Anti-IL-1β/IL-18 Bispecific Monoclonal Antibody

Introduction:

Current evidence suggests that a dysregulated host innate immune response to SARS CoV-2 may play a role in the development of a hyper-inflammatory syndrome during COVID-19. Targeted treatment with inhibitors of key inflammasome-related effector cytokines may safely reduce underlying inflammation.

Method:

Here we present results from a Ph2 RCT in hospitalized SARS-Cov-2 infected patients with moderate to severe COVID-19 pneumonia and inflammation (NCT04382651). Eligible patients were randomized to a single IV infusion of MAS825, an anti-IL-1β/IL-18 bispecific monoclonal antibody or matching placebo in addition to standard of care (SoC). Key study endpoints included evaluation of safety, CRP, SARS-CoV-2 presence and pathway inflammatory markers.

Results:

Patients (n=138) were randomly assigned to receive SoC and either MAS825 (n=68) or placebo (n=70). MAS825 used in conjunction with SoC was safe and well tolerated. There were no MAS825-related adverse events (AEs) or serious AEs. Compared with placebo, MAS825 resulted in earlier clearance of virus. MAS825 treated patients showed a 51% decrease in CRP levels, 42% lower IL-6 levels, a 19% decrease on neutrophil levels and 16% lower interferon-γ levels on Day 15 compared with placebo, indicative of IL-1β and IL-18 pathway engagement.

Conclusion:

MAS825 used in conjunction with SoC was safe and well tolerated, inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance in COVID-19 pneumonia patients when compared with placebo.