Efficacy and safety of MAS825 (anti-IL-1ꞵ/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function.
Clinical and experimental immunology
california; plcmmc; covid-19
MAS825, a bispecific IL-1⍰/IL-18 monoclonal antibody, could improve clinical outcomes in COVID19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized nonventilated patients with COVID-19 pneumonia (n=138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on day of discharge (whichever was earlier) with worst case imputation for death. Other study endpoints included safety, Creactive protein (CRP), SARS-CoV2 presence and inflammatory markers. On Day 15, the APACHE II score was 14.5±1.87 and 13.5±1.8 in the MAS825 and placebo groups, respectively (P=0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days) and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.
Critical Care Medicine
Hakim, Alex D; Awili, Mustafa; O'Neal, Hollis R; Siddiqi, Omar; Jaffrani, Naseem; Lee, Richard; Overcash, Jeffrey S; Chauffe, Ann; Hammond, Terese C; Patel, Bela; Waters, Michael; Criner, Gerard J; Pachori, Alok; Junge, Guido; Levitch, Rafael; Watts, Jen; Koo, Philip; Sengupta, Tirtha; Yu, Lili; Kiffe, Michael; Pinck, Anne; Stein, Richard R; Bendrick-Peart, Jamie; Jenkins, Janet; Rowlands, Marianna; Waldron-Lynch, Frank; and Matthews, Jesse, "Efficacy and safety of MAS825 (anti-IL-1ꞵ/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function." (2023). Articles, Abstracts, and Reports. 7438.