Adrecizumab: an investigational agent for the biomarker-guided treatment of sepsis.

Introduction: Sepsis is a major health problem with a high incidence and mortality. ADM, a free-circulating peptide mainly expressed and secreted by vascular endothelial cells, shows vasodilatory properties and causes hypotension when present in higher concentrations during sepsis. Areas covered: Adrecizumab (ADZ) (HAM 8101) is a humanized targeted therapy directed against the N-terminus of adrenomedullin (ADM). ADZ inhibits excessive circulating sepsis-induced ADM and stimulates protective effects on the endothelial barrier, and decreases interstitial vasodilatory effects. ADZ demonstrated a promising safety profile in healthy subjects in phase I studies. According to these results, a phase II proof of concept study enrolling 300 septic patients is currently in course (NCT03085758). Expert opinion: ADZ is the first humanized antibody directed against ADM. The main interest of ADZ is its potential use as a 'biomarker-guided therapy' in septic patients with high circulating ADM. ADZ is increasingly seen as a potential adjunct therapy to restore endothelial function in septic shock. A positive pivotal phase III trial is indeed needed to convince the intensive care community to prescribe ADZ in septic shock patients. Further, it would be of interest to see whether ADZ might also benefit other critical diseases such as cardiogenic shock where endothelial dysfunction has also been described.