An In-Depth Review of MDX-018 (HuMax-Inflam / BMS-986253): A Therapeutic Antibody Targeting Interleukin-8

1. Executive Summary

MDX-018, an investigational therapeutic agent, is a fully human monoclonal antibody specifically designed to target and neutralize interleukin-8 (IL-8), a pivotal chemokine implicated in a spectrum of human diseases. Known by various designations including HuMax-Inflam, HuMax-IL8, BMS-986253, and Adakitug, this antibody has undergone extensive evaluation across a diverse range of clinical indications. These encompass oncological conditions such as glioblastoma, various other solid tumors (including liver cancer and non-small cell lung cancer - NSCLC), and inflammatory disorders like palmoplantar pustulosis, chronic obstructive pulmonary disease (COPD), myelodysplastic syndromes (MDS), and even infectious complications such as those seen in COVID-19.

The primary mechanism of action of MDX-018 involves binding to IL-8, thereby preventing its interaction with its cognate receptors, CXCR1 and CXCR2. This blockade effectively abrogates IL-8-mediated signaling, which is known to drive neutrophil recruitment, sustain inflammation, promote angiogenesis, and contribute to tumor progression and immune evasion.

The clinical development of MDX-018 has been characterized by a complex trajectory, involving multiple pharmaceutical entities including Genmab, Medarex, and Bristol-Myers Squibb. While some therapeutic avenues, such as palmoplantar pustulosis and glioblastoma, have been discontinued despite early promising signals, research and clinical trials have continued or completed in other areas, notably in solid tumors, MDS, and COVID-19. The safety profile of MDX-018 has generally been reported as manageable in several studies, particularly as a monotherapy, although the adverse event landscape becomes more complex when used in combination regimens, aligning with expectations for multi-agent immunotherapies.