IPTACOPAN DEMONSTRATES SUSTAINED EFFICACY AND SAFETY IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: UP TO 4 YEARS OF FOLLOW-UP IN PATIENTS FROM APPLY, APPOINT AND ROLL-OVER EXTENSION PROGRAM
Régis Peffault de Latour et al
Université Paris Cité, Saint‑Louis Hospital, Paris, France
Background
- Iptacopan demonstrated sustained hematologic control and a favorable safety profile in patients with paroxysmal nocturnal hemoglobinuria (PNH) in phase 3 studies APPLY-PNH (NCT04558918) and APPOINT-PNH (NCT04820530), with efficacy and safety maintained from 24-48 weeks in the parent studies to 2 years in the roll-over extension program (PNH-REP; NCT04747613).
- The aim of the study is to assess the long-term safety and efficacy of iptacopan monotherapy in patients with PNH who initiated treatment with iptacopan in APPLY-PNH and APPOINT-PNH with up to 4 years’ follow-up.
Methods
- All patients received iptacopan monotherapy 200 mg twice daily across parent studies and PNH-REP; the first dose in parent study was considered as baseline (BL). Efficacy assessments included hemoglobin (Hb), lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), transfusion avoidance, breakthrough hemolysis (BTH) rates and prevention of major adverse vascular events (MAVEs).
- Safety assessments included treatment-emergent adverse events and serious adverse events (SAEs).
Results
- At data cut-off, study participation was completed or ongoing in 122/136 patients (89.7%). Hematologic efficacy was sustained, with results comparable across 2, 3 and 4 years (Figure). At 3 and 4 years, mean (SD) Hb was 12.9 g/dL (1.8) and 12.3 g/dL (1.5), respectively, with Hb ≥12.0 g/dL achieved in 76/104 (73.1%) and 14/20 patients (70.0%), irrespective of blood transfusion.
- Control of intravascular hemolysis was maintained, with LDH levels <1.5×ULN in 95/105 patients (90.5%) at 3 years and 18/19 (94.7%) at 4 years. Markers of extravascular hemolysis showed improvement; mean (SD) ARC decreased by −100.9 (69.1) and −114.7×109/L (55.8) at 3 and 4 years, with ARC normalization observed in 96/104 (92.3%) and 18/19 patients (94.7%), respectively. Mean (SD) changes from BL for bilirubin at 3 and 4 years were −18.3 µmol/L (23.4) and −15.1 µmol/L (9.8), respectively.
- Mean (SD) changes from BL in platelet count were −10.3×109/L (52.8) and −11.2×109/L (46.1), respectively. Overall, 118/136 patients (86.8%) remained transfusion-free throughout the treatment period. Mean (SD) FACIT-F score improvements from BL were 9.3 (10.8) and 8.2 (9.1) at 3 and 4 years, respectively.
- There were 37 BTH events in 23 patients (8.3 events/100 patient years [py]), including 6 serious events (1.3 events/100 py); all events resolved, and no BTH led to treatment discontinuation. Six MAVEs occurred in 5 pts (1.3 events/100 py), including 3 severe events in 2 patients; 1 event of intestinal infarction resulted in death.
- SAEs occurred in 50/136 patients (36.8%), including serious infections and infestations in 24/136 patients (17.6%; 8.7/100 py). Five deaths (3.7%) occurred due to cardiopulmonary failure following sepsis, gastrointestinal hemorrhage, metastatic colorectal cancer, pneumonia, and infection with ascites followed by intestinal infarction.
- No death was related to iptacopan treatment. Nine pregnancies were reported; of these, 4 resulted in elective abortions, 2 in spontaneous abortions, 1 in ectopic pregnancy and 2 in healthy live births.
Conclusion
- With up to 4 years of follow-up, iptacopan monotherapy demonstrated sustained efficacy, with hemolysis control, high transfusion avoidance, and improved fatigue in patients with PNH. Long-term treatment was well tolerated, with no new safety findings.
