THE 2-YEAR SAFETY and EFFICACY of IPTACOPAN MONOTHERAPY in PATIENTS with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) from APPLY- and APPOINT-PNH STUDIES WHO ENTERED the ROLL-OVER EXTENSION PROGRAM (REP).
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All Authors
Risitano, A.
Kulasekararaj, A.
Scheinberg, P.
Ueda, Y.
Roth, A.
Han, B.
Zhang, L.
Di Bona, E.
Fu, R.
Griffin, M.
LTHT Author
Griffin, Morag
Kelly, Richard
Kelly, Richard
LTHT Department
Oncology
Haematology
Haematology
Contributor Profession (Non Medical)
Publication Date
2025
Item Type
Conference Abstract
Language
Subject
Subject Headings
Abstract
Background Iptacopan, an oral factor B inhibitor approved as a monotherapy for treatment of adults with PNH, provided sustained improvement of hemoglobin (Hb) to near-normal levels, transfusion independence (TI), and decreased patient-reported fatigue in patients (pts) with persistent anemia despite anti-C5 treatment (APPLY-PNH; NCT04558918) or who were complement inhibitor naive (APPOINT-PNH; NCT04820530). Results from these phase 3 trials showed that the efficacy of iptacopan observed at Week (wk) 24 was sustained up to wk 48. The oral delivery method and the unique mechanism of action of iptacopan offer potential benefits over current treatments, warranting an assessment of its long-term therapeutic outcomes. Aims The purpose of the current analysis is to assess the long-term safety, tolerability, and efficacy of iptacopan monotherapy in pts with PNH who started treatment with iptacopan in APPLY- and APPOINT-PNH studies. Herein, we report the 2-year follow-up data. Methods The REP (NCT04747613) is an ongoing, open-label, single-arm, multicenter, phase 3 study involving 59 centers globally. It enrolled pts, who completed phase 2 and 3 trials and benefited from iptacopan treatment, serving as the source for the current analysis. Results Out of 136 pts treated with iptacopan in APPLY- and APPOINT-PNH, 128 (94.1%) were still on treatment at 2-year follow-up, 8 (5.9%) having discontinued treatment due to pregnancy (2), physicians' decision (2), adverse events (AEs) (1), delayed Institutional Review Board approval (1), and death (2). In this combined analysis set, 71.8% (89/124) pts achieved a sustained Hb of >=12 g/dL, while 83.9% (104/124) had an Hb increase of >=2 g/dL, both irrespective of RBC transfusions at 2 years. Mean (SD) Hb level (irrespective of RBC transfusion) at 2 years was 12.69 g/dL (2.022), with mean (SD) change from baseline (BL) of 3.9 g/dL (2.461). Mean (SD) LDH level was 300.37 (196.565) U/L. LDH <1.5 x ULN was observed in 88.7% (110/124) pts. TI was achieved in 90.4% pts. Mean (SD) Functional Assessment of Chronic Illness Therapy-Fatigue score was 43.0 (8.97) with mean change (SD) from BL of 10.0 (11.18). Overall, efficacy results were comparable among the APPLY-PNH REP, APPOINT-PNH REP, and the combined arms (Table). The exposure-adjusted reporting rate of serious AEs (SAEs: 24.7 per 100 pt-years) during 2 years of treatment was similar to that observed in APPLY- and APPOINT-PNH over 24 wks (28.0 and 20.7 per 100 pt-years, respectively). The most common treatment-emergent AEs (reported in >=10% of pts) were COVID-19 (46.3%), headache (21.3%), diarrhea (19.1%), upper respiratory tract infection (17.6%), nasopharyngitis (16.9%), abdominal pain (12.5%), nausea and vomiting (each 11.8%), pyrexia and breakthrough hemolysis [BTH] (each 11.0%). The low exposure-adjusted rate of serious BTH over 2 years (1.1 events per 100 pt-years) was consistent with no serious BTH observed during 24 wks and 1 serious BTH during 48 wks. Major adverse vascular events were observed in 3 pts (4 events). Summary/Conclusion The 2-year data showed that iptacopan was well tolerated with no new safety signals and no increase in exposure-adjusted rates of AEs or SAEs with longer treatment duration. Sustained Hb >= 12 g/dL and LDH <1.5 x ULN in majority of pts at 2-year reflect comprehensive hemolysis control with iptacopan, accompanied by improvement in patient-reported fatigue. These findings continue to support oral iptacopan monotherapy as a potentially practice-changing treatment for pts with PNH.
Journal
HemaSphere