2. Academic Validation
  3. Efficacy and safety of MAS825 (anti-IL-1β/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function

Efficacy and safety of MAS825 (anti-IL-1β/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function

  • Clin Exp Immunol. 2023 Oct 13;213(3):265-275. doi: 10.1093/cei/uxad065.
Alex D Hakim 1,  Mustafa Awili 2,  Hollis R O'Neal 3,  Omar Siddiqi 4,  Naseem Jaffrani 5,  Richard Lee 6,  Jeffrey S Overcash 7,  Ann Chauffe 8,  Terese C Hammond 9,  Bela Patel 10,  Michael Waters 11,  Gerard J Criner 12,  Alok Pachori 13,  Guido Junge 14,  Rafael Levitch 14,  Jen Watts 15,  Philip Koo 16,  Tirtha Sengupta 17,  Lili Yu 18,  Michael Kiffe 19,  Anne Pinck 19,  Richard R Stein 19,  Jamie Bendrick-Peart 16,  Janet Jenkins 18,  Marianna Rowlands 18,  Frank Waldron-Lynch 18,  Jesse Matthews 20
Affiliations

Affiliations

  • 1 Providence Little Company of Mary Medical Center, Torrance, CA, USA.
  • 2 Dallas Regional Medical Center, Mesquite, TX, USA.
  • 3 Louisiana State University Health Sciences Center and Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA.
  • 4 Boston Medical Center, Boston, MA, USA.
  • 5 Rapides Regional Medical Center, Alexandria, LA, USA.
  • 6 University of California, Irvine, CA, USA.
  • 7 Sharp Grossmont Hospital, La Mesa, CA, USA.
  • 8 Louisiana State University Health Sciences Center, Lafayette, LA, USA.
  • 9 Saint Johns Cancer Institute, Santa Monica, CA, USA.
  • 10 University of Texas McGovern Medical School, Houston, TX, US.
  • 11 Sharp Chula Vista Medical Center, Chula Vista, CA, USA.
  • 12 Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  • 13 MorphoSys AG, Boston, MA, USA.
  • 14 Novartis Pharma AG, Basel, Switzerland.
  • 15 Oculis, Boston, MA, USA.
  • 16 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
  • 17 Novartis Healthcare Pvt Ltd, Hi-Tech City, Hyderabad, India.
  • 18 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • 19 Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • 20 Hospital Medicine, St Charles Health System, Bend, OR, USA.
PMID: 37338154 DOI: 10.1093/cei/uxad065
Abstract

MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated 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 the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 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 COVID-19 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.

Keywords

COVID-19; MAS825; efficacy and safety; impaired respiratory function; pneumonia.

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