Ravulizumab in the treatment of paroxysmal nocturnal hemoglobinuria

ABSTRACT

Introduction

Eculizumab, the anti-C5 monoclonal antibody therapeutic, has revolutionized the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and has shown efficacy in other complement-mediated disorders including atypical Hemolytic Uremic Syndrome (aHUS) and Myasthenia Gravis (MG). Despite the effectiveness of eculizumab, challenges remain in the treatment of these diseases, including breakthrough hemolysis, frequent intravenous infusions, and cost; in an effort to mitigate these challenges, the new monoclonal therapeutic ravulizumab has been developed.

Areas covered

In this paper, we review the characteristics and clinical performance of ravulizumab and assess its potential utility in the treatment of PNH, and its position in this rapidly-developing therapeutic landscape. A review of published data up to Phase III of ravulizumab had been performed. Studies were identified via Google Scholar, PubMed, the United States National Library of Medicine Clinical Trials, citation chasing, and topic knowledge of the authors.

Expert opinion

Ravulizumab represents an important advance in the clinical care of complement-mediated disorders. Clinical trials demonstrate non-inferior efficacy and indistinguishable safety and tolerability to eculizumab, with added patient-preferred benefits including longer intervals between infusions. Though improved, physicians should be aware of the limitations of ravulizumab, including the need for intravenous infusions and possible breakthrough hemolysis.

KEYWORDS:

• Paroxysmal nocturnal hemoglobinuria
• PNH
• complement
• eculizumab
• ravulizumab
• atypical hemolytic uremic syndrome
• aHUS
• myasthenia gravis
• MG

Article Highlights

• Eculizumab, an anti-C5 monoclonal antibody therapeutic, is an effective therapy for Paroxysmal Nocturnal Hemoglobinuria (PNH).

• It is an emerging therapeutic consideration for other complement-mediated disorders including atypical Hemolytic Uremic Syndrome (aHUS) and Myasthenia Gravis (MG)

• Ravulizumab is a new anti-C5 monoclonal antibody therapeutic with longer half life than eculizumab.

• Ravulizumab demonstrates non-inferior efficacy and indistinguishable safety and tolerability to eculizumab, with added patient-preferred benefits including longer intervals between infusions.

Declaration of interest

R Wells receives honoraria from Alexion Pharmaceuticals has been an investigator in the clinical trials for Ravulizumab. The authors have 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.