Safety and efficacy of danicopan in patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated intravascular hemolysis (IVH). Current treatments like Eculizumab and Ravulizumab have limitations, with many patients still requiring transfusions. This study aimed to investigate the safety and efficacy of the new emergent treatment called Danicopan.

Methods: We systematically searched five electronic databases - Epistemonikos, Web of Science, Medline, Scopus, and ClinicalTrials - to ensure comprehensive coverage. The systematic review was conducted following the PRISMA guidelines, ensuring methodological rigor.

Results: Four studies were eligible for inclusion, all of them were multicenter trials with 79 patients studied. Treatment with Danicopan led to a notable improvement in hemoglobin levels and a decrease in reticulocyte counts. However, LDH levels did not significantly change after treatment. Additionally, there was a significant increase in GPI-deficient erythrocytes but not in GPI-deficient granulocytes. Total and direct bilirubin levels showed significant differences between treatment groups, and there was an improvement in FACIT scores from baseline.

Conclusions: Our systematic review and meta-analysis support the potential of Danicopan as a viable therapeutic option for PNH patients. The targeted inhibition of factor D within the complement system by Danicopan demonstrates both safety and efficacy in managing PNH, as evidenced by our findings.

Registration: This paper was registered with the PROSPERO database (CRD42024499375).