Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated intravascular hemolysis. Current treatments like Eculizumab and Ravulizumab have limitations, with many patients still requiring transfusions. Danicopan is a first-in-class oral small molecule drug that inhibits the complement alternative pathway component D. The drug has shown efficacy in suppressing intravascular hemolysis and controlling C3-mediated extravascular hemolysis, which may reduce the side effects of conventional treatments. This study aimed to investigate the safety and efficacy of Danicopan, a newly FDA-approved add-on treatment for PNH.

We systematically searched five electronic databases to ensure comprehensive coverage: Epistemonikos, Web of Science, Medline, Scopus, and ClinicalTrials. Meta-analysis was conducted through the "R" language with the "meta" statistical package.

Four multicenter trials involving 79 patients were included. Danicopan treatment significantly improved hemoglobin levels (SMD 1.536, 95% CI: 0.683 to 2.390, p < 0.001) and decreased reticulocyte counts (SMD -0.996, 95% CI: -1.352 to -0.641, p < 0.001). However, LDH levels did not significantly change after treatment. There was a significant increase in GPI-deficient erythrocytes but not in granulocytes. Both total and direct bilirubin levels showed significant differences from baseline to week 12 after treatment. Additionally, there was a notable improvement in FACIT scores from baseline.

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.

Ethics Approval: Not applicable.

Funding information: None.

Conflict of Interest Statement: The authors declare no competing interests.

Data availability Statement: The data supporting this study"s findings are available from the corresponding author upon reasonable request.

Author contributions: Study concept and design: Emir Muvaffak, Muhammed Edib Mokresh; screening: Emir Muvaffak, Muhammed Edib Mokresh, Abdullah Varda; acquisition of data: Emir Muvaffak, Muhammed Edib Mokresh, Abdullah Varda, Mahmoud Lakmoush; analysis and interpretation of data: Muhammed Edib Mokresh, Merve Kabasakal Ilter; drafting of the manuscripts: All authors participated; critical revision of the manuscript: All authors participated.