Safety and Efficacy of Corvalimab in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Single-Arm Meta-Analysis

Title: Safety And Efficacy of Crovalimab in Paroxysmal Nocturnal

Hemoglobinuria (PNH): A Systematic Review and Single-arm Meta-analysis

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is rare, genetic, life-threatening

haematological disease affecting 12-13 individuals per 1 million worldwide, caused by mutation

in PIGA gene. PNH is associated intravascular haemolysis, thrombosis and pancytopenia with up

to 35% 5-year mortality rates. Crovalimab, a novel FDA-approved C5 inhibitor, appeared to

promising therapy for C5 mutation patients with less effective outcomes on conventional

therapies.

Objective: To evaluate the safety and efficacy of Crovalimab in paroxysmal nocturnal

hemoglobinuria (PNH).

Methods: The PubMed, Embase, Scopus and Cochrane databases were systematically searched

using relevant keywords from inception until July 2024. A total of 3 studies fulfilling predefined

selection criteria were included. We performed meta-analysis of prevalence using MetaXL

Software (version 5.3). We pooled the prevalence rate presented as untransformed proportion

with the corresponding 95% confidence interval (CI) using the random effects model. The I2 and

X2 statistics were used to evaluate interstudy heterogeneity. A heterogeneity of I2 > 50% was

considered significant.

Results: We found the pooled prevalence of ≥1 any-grade adverse event (AE) of any cause 92%

(95% CI 0.76-1.00,I2=85%) and serious adverse event of any cause 15% (95% CI 0.05-0.29,

I2=75%). We found the pooled prevalence of ≥1 treatment-related any-grade AE 47% (95% CI

0.20-0.75, I2=91%) and serious AE 3% (95% CI 0.01-0.06, I2=0%).The pooled prevalence of the

patients with hemolysis control was 79% (95% CI 0.73-0.84, I2=0%), post-baseline transfusion

avoidance 59% (95% CI 0.50-0.68, I2=19%), stabilized hemoglobin 59% (95% CI 0.46-0.71,

I2=59%) and breakthrough hemoglobin 9% (95% CI 0.06-0.13, I2=0%)

Conclusion: We found that crovalimab showed less prevalence of both any-cause and treatment-

related adverse events, a high proportion of patients with controlled hemolysis, post-baselines

transfusion avoidance and stabilized hemoglobin in patients with PNH. Moreover, only a small

proportion of patients had breakthrough hemoglobin. More robust studies with larger sample

sizes are required to establish conclusive evidence.

No relevant conflicts of interest to declare.