REAL-WORLD OUTCOMES OF IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) PATIENTS: INSIGHTS FROM THE FRENCH EARLY ACCESS PROGRAM
Edouard Forcade et al
CeRAMIC, CHU Bordeaux, Hopital Haut-Leveque, Pessac, France
Background
- Iptacopan is the 1st oral monotherapy targeting Factor B to inhibit the proximal alternative complement pathway, effectively controlling both intra and extravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). In the APPLY-PNH randomized trial, iptacopan was superior to antiC5 therapies (C5i) in improving hemoglobin (Hb) and reducing red blood cell transfusion (RBCT) in patients with persistent anemia.
- Since May 2, 2024, an Early Access Program (EAP) have enabled iptacopan access in France for adults with PNH with anemia despite C5i.
The aim of the study is to report the real-world effectiveness and safety of iptacopan in France.
Methods
- Eligibility criteria were adult patients with PNH clone size ≥10% and Hb <10 g/dL despite 6 months of C5i. Patients intolerant to 2nd line proximal inhibitor (C3i) were eligible if previously received ≥6 months of C5i with Hb <10 g/dL at switch.
- Treatment initiation required vaccination and validation by the French reference center multidisciplinary team.
- Clinical and biological data are collected at treatment request, initiation and subsequently at day 15 (D15), month 2 (M2), and every 2 months during year 1, then every 4 months thereafter.
Results
- Overall, 51 initiated iptacopan and were included by 22 physicians (mean age 47.9 ± 17.9 years; 64.7% women). Prior thrombotic events were reported for 15 patients (29.4%). Among these patients, 4 had previously started iptacopan through compassionate access and 7 initiated treatment following intolerance to a 2nd line C3i. These 11 patients had Hb >10 g/dL at treatment request. Among the other 40 patients previously treated by C5i, RBCT in the 12 months preceding treatment was required for 22 patients (55.5%) (mean number transfusions per patient: 10.6 ± 10.1). Mean exposure to iptacopan was 7.6 ± 4.5 months (min: 0; max: 17.4 months).
- In the Hb ≤10 g/dL subgroup (N=40), mean (±SD) Hb increased significantly and rapidly from baseline (8.65 ± 0.97 g/dL) by 3.01 ± 1.79 g/dL (11.66 ± 1.53 g/dL) at D15, followed by progressive increases at subsequent visits:+4.44 ± 1.40 g/dL at M6 (13.07 ± 1.11 g/dL), and +4.60 ± 1.92 at M12 (13.26 ± 1.44 g/dL). Transfusion independence increased from 50% at baseline to 95% at D15 and 100% at M12. In the Hb >10 g/dL subgroup (N=11), mean Hb (baseline: 12.30 ± 0.95 g/dL) increased by 0.56 ± 0.81 at D15, and by 0.99 ± 1.24 at M2 and then remained stable, exceeding 13g/dL during follow-up, demonstrating durable long‑term control in this previously treated population. All patients were transfusion independent from D15.
- No death, thromboembolic events or breakthrough hemolysis (BTH) were reported. Overall, 6 patients experienced a total of 16 serious adverse drug reactions (ADR) and 9 non-serious. Two serious infections (pneumonia and cystitis) were reported. Of the 4 patients experiencing serious ADRs two achieved full recovery, one was reported as condition improving, and the remaining case had no documented outcome. None of the ADR resulted in modification or discontinuation of iptacopan.
Conclusion
- The EAP confirms the real-world effectiveness and safety of iptacopan demonstrated in the clinical trials.
- Patients with Hb <10 g/dL showed rapid and sustained Hb improvement with markedly reduced transfusion needs from D15, while patients with prior iptacopan or C3i treatment with Hb >10 g/dL remained stable without BTH reported. Overall, no new safety signals were identified.