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- Title
Crovalimab for treatment of patients with paroxysmal nocturnal haemoglobinuria and complement C5 polymorphism: Subanalysis of the phase 1/2 COMPOSER study.
- Authors
Nishimura, Jun‐ichi; Usuki, Kensuke; Ramos, Julia; Ichikawa, Satoshi; Buri, Muriel; Kiialainen, Anna; Sostelly, Alexandre; Peffault de Latour, Régis; Paz‐Priel, Ido; Röth, Alexander
- Abstract
One patient had two SAEs (bile duct stone and cholelithiasis) that were not treatment related, and the other had a treatment-related SAE (upper respiratory tract infection) that resolved while on treatment. Keywords: anti-C5 inhibitor; C5 polymorphism; COMPOSER; crovalimab; paroxysmal nocturnal haemoglobinuria EN anti-C5 inhibitor C5 polymorphism COMPOSER crovalimab paroxysmal nocturnal haemoglobinuria e46 e50 5 07/27/22 20220801 NES 220801 Paroxysmal nocturnal haemoglobinuria (PNH) is characterised by the loss of complement regulators CD55 and CD59 on peripheral blood elements, which can result in intravascular haemolysis and thrombosis.1 C3 (pegcetacoplan) and C5 (eculizumab and ravulizumab) inhibitors are approved therapies for PNH and can control intravascular haemolysis in patients with PNH.2-5 However, eculizumab and ravulizumab lack efficacy in patients with inherited nonsynonymous polymorphisms in the C5 subunit (i.e. c.2654G -> A and c.2653C -> T) affecting Arg885, which corresponds to their target epitope.5,6 Such polymorphisms are present in <=3.5% of individuals of Asian descent and have been reported in a patient with no known Asian ancestry.5-8 Hence, patients with PNH and C5 polymorphism have a high unmet clinical need.5,6 The newly approved C3 inhibitor pegcetacoplan, which blocks the complement cascade upstream of C5, may be effective in treating these patients, but specific data are unavailable.2 Therefore, these patients should be enrolled in an appropriate study. Overall, the response to previous therapy in these patients with C5 SNP was consistent with the typical poor haemolysis control experienced with eculizumab or ravulizumab in such patients.5,6 With crovalimab treatment, all four patients achieved sustained terminal complement inhibition and haemolysis control consistent with all patients in COMPOSER.10 Three serious adverse events (SAEs) were reported in two patients.
- Subjects
PAROXYSMAL hemoglobinuria; COMPLEMENT (Immunology)
- Publication
British Journal of Haematology, 2022, Vol 198, Issue 3, pe46
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.18274