I-Mab reports positive interim analysis from phase II/III study of its GM-CSF antibody plonmarlimab (TJM2) | medthority.com

Plonmarlimab was discovered and developed by I-Mab to target human granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that plays a critical role in acute and chronic inflammation.

The ongoing U.S. phase II/III study is one of the first double-blind, placebo-controlled, randomized studies to evaluate the therapeutic role of GM-CSF antibody in severe COVID-19 patients. The study aimed to determine the safety, efficacy and effects on cytokine levels following a single dose of 6 mg/kg of plonmarlimab or placebo in patients with severe COVID-19.

The current interim analysis showed positive preliminary results in patients who were mechanical ventilation free (MVF) at baseline (N=91). Plonmarlimab treatment resulted in a higher MVF rate (83.6% vs 76.7%) by day 30, lower mortality rate (4.9% vs 13.3%) by day 30, higher recovery rates (68.9% vs 56.7% at day 14 and 80.3% vs 70.0% at day 30), as well as reduced time to recovery and hospitalization duration, as compared to placebo. The magnitudes of the clinical improvements are comparable to those observed with lenzilumab in a similar patient population.

Biomarker results were consistent with the observed clinical outcome and indicated patients treated with plonmarlimab had a reduction in plasma levels of pro-inflammatory cytokines and chemokines critically involved in CRS, including TARC, IP10, GCSF, IL10, IL6, MCP1, IL1RA, TNF-alpha but not interferon-gamma. A transient increase in Neutrophil to Lymphocyte Ratio (NLR) that is commonly associated with disease exacerbation was only observed in placebo. Plonmarlimab was well tolerated in all patients with no significant safety concerns.