Pharmacological and clinical profile of ravulizumab 100 mg/mL formulation for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

ABSTRACT

Introduction

Paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) are two rare and severe conditions caused by chronic complement (C’) system dysregulation. Treatment with eculizumab, a recombinant, humanized monoclonal antibody against complement C5, changed the natural history of both diseases inducing remission and improving patient outcome. Ravulizumab, a new long-acting next-generation C5 inhibitor, has been recently approved for treatment of PNH and aHUS.

Areas covered

Main characteristics of ravulizumab are described: composition, dosing, efficacy and safety profile. Further, an overview of seminal studies and clinical trials using ravulizumab to treat PNH and aHUS in children and adults is detailed. Literature review was performed using the following key words: paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and ravulizumab.

Expert opinion

Ravulizumab profile to treat PNH and aHUS is equivalent to eculizumab in efficacy and safety but allows extended dosing interval to every 4–8 weeks based on patient weight, and requires reduced infusion time. Less travels to infusion centers and medical visits and decreasing job and school absences significantly increase patient and families’ QoL, while reducing cost. Further infusion time is reduced. Ravulizumab will possibly become the treatment of choice for patients with PNH and aHUS on chronic C5 inhibition.

KEYWORDS:

• Complement
• paroxysmal nocturnal hemoglobinuria
• atypical hemolytic uremic syndrome
• ravulizumab
• eculizumab
• quality-of-life

Article highlights

• Ravulizumab is a new long-acting next-generation C5 inhibitor recently approved for treatment of PNH and aHUS which is administered intravenously in intervals of 4 to 8 weeks based on patient-weight

• Ravulizumab´s profile to treat PNH and aHUS is equivalent to eculizumab’s in efficacy and safety

• Treatment with ravulizumab improves patient and caregivers’ QoL and reduces costs

Declaration of interest

G Ariceta declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Alexion (Astra Zeneca Rare Diseases), Recordati Rare Diseases, Advicenne, Chiesi, Kyowa Kirim, Alnylam; participation on a Data Safety Monitoring Board or Advisory Board: Alexion (Astra Zeneca Rare diseases), Dicerna, Advicenne, Alnylam; support for attending meetings and/or travel: Recordati Rare Diseases, Advicenne, Kiowa Kirim; Cochair of the Scientific Advisory Board of aHUS Global Registry supported by Alexion (Astra Zeneca Rare Diseases). 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a coauthor and investigator on several of the papers referenced in this article. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Company review

Alexion Pharmaceuticals provided a scientific accuracy review at the request of the journal editor.

Information resources

Additional information regarding treatment with ravulizumab in PNH and aHUS patients can be found at the following websites:

• https://www.clinicaltrials.gov/ct2/results?cond=&term=RAVULIZUMAB&cntry=&state=&city=&dist=

• https://www.ema.europa.eu/en/medicines/human/EPAR/ultomiris

• https://alexion.com/en/our-medicines/medicines/ultomiris

Additional information

Funding

This paper was not funded.