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Review
. 2024;16(20-22):1185-1196.
doi: 10.1080/1750743X.2024.2433410. Epub 2024 Dec 2.

Crovalimab in the paroxysmal nocturnal hemoglobinuria treatment landscape

Alexander Röth  1 , Austin G Kulasekararaj  2   3   4 , Phillip Scheinberg  5 , Jun-Ichi Nishimura  6
Affiliations
Review

Crovalimab in the paroxysmal nocturnal hemoglobinuria treatment landscape

Alexander Röth et al. Immunotherapy. 2024.

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, rare, life-threatening hematopoietic stem cell disorder that causes stem cell-derived cells to be vulnerable to complement-mediated lysis and manifests as hemolytic anemia, thrombosis, and peripheral blood cytopenias. C5 inhibitors, eculizumab, and ravulizumab, are recognized as the current standard of care for PNH treatment in countries where they are available. Crovalimab (PiaSky®), which is approved for the treatment of PNH, is a novel anti-C5 inhibitor with an every-4-weeks, low-volume, subcutaneous maintenance dosing regimen with the possibility for self-administration. Data from three phase III studies highlight the overall favorable benefit-risk profile of crovalimab, showing that crovalimab has promising potential to address the unmet medical and socioeconomic challenges in the PNH treatment landscape.

Keywords: Crovalimab; PNH; anti-C5 recycling monoclonal antibody; complement inhibitor; every-4-weeks dosing; paroxysmal nocturnal hemoglobinuria; subcutaneous self-administration.

Plain language summary

Paroxysmal nocturnal hemoglobinuria or PNH is a rare, life-threatening blood disorder that leads to the breakdown of red blood cells. People with PNH can have symptoms including tiredness, headaches, less appetite, and difficulty concentrating. Where available, the most common treatment for PNH is a type of medicine called a “C5 inhibitor.” C5 inhibitors block (inhibit) C5, one of the proteins that allow red blood cells to be destroyed. Crovalimab (Piasky®) is a new C5 inhibitor taken once every four weeks, mostly as an injection under the skin (subcutaneous injection) at home or in a healthcare setting. Data from three large studies showed that crovalimab had an overall benefit and might help with some of the challenges that still exist for people with PNH.

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Conflict of interest statement

A Röth is a consultant to Alexion Pharmaceuticals, Amgen, Apellis, Bioverativ, BioCryst, F. Hoffmann-La Roche Ltd, Kira, Novartis, Sanofi, and Sobi; received research funding from Roche; and received honoraria from Alexion, F. Hoffmann-La Roche Ltd, Grifols, Sanofi, and Sobi.

AG Kulasekararaj is a consultant to Alexion/AstraZeneca Rare Disease, Amgen, BioCryst, Celgene, F. Hoffmann-La Roche Ltd, Novartis, Novo Nordisk, Pfizer, Samsung, and Sobi; received research funding (to institute) from Celgene/Bristol Myers Squibb and Novartis; received honoraria from Agios, Alexion/AstraZeneca Rare Disease, Amgen, BioCryst, Celgene/Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, Novartis, Novo Nordisk, Pfizer, Ra Pharma, Samsung, and Sobi; and participated in speakers bureau for Alexion/AstraZeneca Rare Disease, Amgen, Celgene, F. Hoffmann-La Roche Ltd, Novartis, Novo Nordisk, Pfizer, Samsung, and Sobi

P Scheinberg is a consultant to AbbVie, Alexion, AstraZeneca, BioCryst, F. Hoffmann-La Roche Ltd, Janssen, and Pfizer; received research funding from Alnylam and Pfizer; and participated in speakers bureau for Alexion, Amgen, AstraZeneca, Bristol Myers Squibb, Novartis, and Pfizer.

J Nishimura received research funding from Alexion and F. Hoffman-La Roche Ltd; received honoraria from Alexion; holds the patent and royalties of WO2020/027279 (anti-C5 antibody dosage regimen); and is a member of the Board of Directors or advisory committees of Alexion, BioCryst Pharmaceuticals, Chugai Pharmaceutical Co., Ltd, F. Hoffmann-La Roche Ltd, Novartis, Sanofi K.K., and Sobi.

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.

Medical writing support was provided by Bena Lim, PhD, CMPP, from Nucleus Global, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Figures

Figure 1.
Figure 1.
Mechanism of action of crovalimab [77].
Figure 2.
Figure 2.
Formation of transient immune complexes when switching between C5 inhibitors.
See this image and copyright information in PMC

References

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