Complement inhibition for paroxysmal nocturnal hemoglobinuria: where we stand and where we are going

Abstract

Introduction: The treatment of paroxysmal nocturnal hemoglobinuria (PNH) has been drastically changed by the introduction of the first therapeutic complement inhibitor eculizumab: 13 years of clinical experience have clearly proven that clinical complement inhibition is feasible, safe and potentially effective. At the same time, a number of observations have been collected showing that current anti-complement treatment is suitable for further improvements, especially for PNH, where extravascular hemolysis secondary to the activation of early complement has emerged as a novel unmet clinical need.

Areas covered: Here we discuss publicly available information on second generation of complement therapeutics, which are currently in preclinical or clinical investigations. These agents are characterized by a broad target spectrum, since they inhibit the complement cascade at different levels: indeed, they include agents targeting component 5 as the key event of the terminal effector complement, as well as compounds designed to intercept the early steps of complement activation.

Expert opinion: The field of therapeutic complement inhibition is growing rich with the development of several agents; the most promising approaches have already started their clinical development. It is conceivable that in the near future some of these strategies may offer improved therapeutic options for PNH and other complement-mediated human disorders.

Keywords:

• component 3
• component 5
• complement therapeutics
• compstatin
• eculizumab
• paroxysmal nocturnal hemoglobinuria

Declaration of interest

The author has received research funding from Alexion Pharmaceuticals, Amyndas Pharmaceuticals, Alnylam Pharmaceuticals, Rapharma and Novartis. He is also consultant for Alnylam Pharmaceuticals and Rapharma, and member of an Advisory Board for Alexion. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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