Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of hematopoietic stem cells (HSCs), characterized by complement mediated intravascular hemolysis, thrombosis, and bone marrow failure. The B-factor inhibitor iptacopan (a first-in-class, oral factor B inhibitor) has been approved in China over one year, there were still fewer reports demonstrated the real-world efficacy and adverse events of iptacopan in PNH. This study followed the efficacy and adverse safety of iptacopan in patients with different types of PNH.

Objective: To analysis the efficacy and adverse events of oral Factor B Inhibitors iptacopan for different types of PNH.

Methods: A retrospective study was conducted on the clinical data of 42 PNH patients who received iptacopan from January 2024 to July 2025, and followed up at Shaanxi Provincial People's Hospital. Evaluated the hemoglobin (Hb) level, red-cell transfusion independence, FACIT-F fatigue score, serum lactate dehydrogenase (LDH) levels, bone marrow proliferation, adverse events, etc. Statistical analysis was performed using SPSS20.0. The follow-up deadline was July 20, 2025.

Results:

  • General: Among the 42 patients with PNH, the ratio of male to female was 23:19, median age was 38 (range: 18-65) years, median duration was 4.5 (range: 0.2-15) years. Among them, 26 cases (61.9%) were classic PNH, 16 cases (38.1%) were secondary from severe aplastic anemia (SAA). 5 cases (11.9%) had a history of thrombosis, and 3 cases (7.1%) had accompanied with renal dysfunction. 30 cases (71.4%) were complement inhibitor-naive patients, 12 cases (28.6%) were patients who had failed with anti-C5 treatment and switched to iptacopan, and 27 cases (64.3%) were red-cell transfusion dependent. Median follow-up was 6 (range: 3-12) months.

  • Efficacy of factor B inhibitor iptacopan in patients with different types of PNH.

1) Among 30 complement inhibitor-naive patients, 86.6% (26/30) met the hemoglobin response criteria (Hb≥12g/dL or increase≥2g/dL) after one week with iptacopan. While the 12 patients who failed with anti-C5 treatment switched to iptacopan, 73.1% (9/12) met the hemoglobin response criteria within 12 weeks. 100% (30/30) of complement inhibitor-naive patients achieved LDH normalization (P＜0.001).

In addition, 90.9% (20/22) of complement inhibitor-naive patients met the criteria for red-cell transfusion avoidance during the observation period (19 cases within 4 weeks and 1 case after 12 weeks). At 12 weeks, the quality of life of all complement inhibitor-naive patients significantly improved, with an average increase of 12.3 points in FACIT-F fatigue score (P＜0.001). Among the 12 patients who failed with anti-C5 treatment and switched to iptacopan, 91.6% (11/12) achieved LDH normalization (P＜0.001), 100% (5/5) met the criteria for red-cell transfusion avoidance, and the FACIT-F score increased by an average of 9.7 points (P＜0.001).

2) Among the 26 patients with classical PNH, 88.2% (23/26) met the Hb response criteria within 4 weeks (P＜0.001). 96.2% (25/26) achieved LDH normalization within 4 weeks. All classic PNH patients met the criteria for red-cell transfusion avoidance, and 85.0% (22/26) reported significant improvement in fatigue symptoms (FACIT-F score increased by≥5 points). Among the 16 patients secondary from SAA, 54.9% (9/16) met the Hb response criteria within 4 weeks, and 87.5% (14/16) met the criteria for red-cell transfusion avoidance. 50% (8/16) of patients secondary from SAA showed bone marrow hematopoietic recovery (neutrophil or platelet count increased by≥50%). The FACIT-F scores of all patients secondary from SAA increased by an average of 7.5 points (P=0.002).

  • Safety: 47.6% (20/42) of the patients experienced treatment-related adverse events (TRAEs), but all were mild adverse events of grade 1-2. The most common TRAEs were headache (33.3%, 14/42), joint and muscle soreness (23.8%, 10/42), upper respiratory tract infection (11.9%, 5/42), diarrhea (9.52%, 4/42), and nausea (7.14%, 3/42). 4.76% (2/42) of patients experienced breakthrough hemolysis (BTH). No patients discontinued treatment with iptacopan due to the adverse events.

Conclusion: Oral administration of factor B inhibitor iptacopan in PNH, either in classic or secondary from SAA, with or without anti-C5 treatment, can effectively improve fatigue status, control hemolysis, and most patients can meet the criteria for red-cell transfusion avoidance, with tolerable adverse events.

This content is only available as a PDF.
2025
Sign in via your Institution