Indirect Treatment Comparison of Iptacopan Versus Eculizumab and Ravulizumab for Patients With Paroxysmal Nocturnal Hemoglobinuria Naive to C5 Inhibitors

Author(s)

Peffault de Latour R1, Scheinberg P2, Spin P3, Balp MM4, Pannagl K5, Wiyani A6, Somenzi O4, Snellman J4, Wang P3, Steenkamp J3, Kulasekararaj A7
1French Référence Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France, 2Hospital A Beneficência Portuguesa, São Paulo, Brazil, 3EVERSANA, Burlington, ON, Canada, 4Novartis Pharma AG, Basel, BS, Switzerland, 5Novartis Pharmaceuticals UK Ltd, London, LON, UK, 6Novartis Pharmaceuticals UK Ltd, London, UK, 7King’s College Hospital NHS, London, UK

OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood condition characterized by hemolysis, anemia and thrombosis. Current treatments include complement 5 inhibitor (C5i) infusions, eculizumab or ravulizumab. Iptacopan is the first-in-class, oral monotherapy, factor B inhibitor assessed in C5i-naïve PNH patients. In the absence of head-to-head data, the aim was to conduct an indirect treatment comparison (ITC) of iptacopan vs eculizumab or ravulizumab in this target population.

METHODS: A systematic literature review and ITC feasibility identified Study 301 (NCT02946463; ravulizumab vs eculizumab), as most relevant comparator trial for single-arm APPOINT-PNH (NCT04820530). Unanchored matching-adjusted indirect comparisons were conducted using individual patient data from APPOINT-PNH for iptacopan (N=40) and published aggregate data from Study 301 for eculizumab (N=121) and ravulizumab (N=125). No patients were excluded from APPOINT-PNH dataset due to high degree of overlap in trial eligibility criteria. Patients were re-weighted via entropy balancing to match patient characteristics in Study 301, adjusting for age, gender, % transfusion-free 12 months prior, lactate dehydrogenase (LDH) at baseline and history of major adverse vascular events. Outcomes assessed were change from baseline (CFB) in LDH and transfusion avoidance and their definition was aligned across studies to the extent possible.

RESULTS: After matching and adjusting, baseline characteristics were similar, with an effective sample size of 31 for APPOINT-PNH. The mean difference in % CFB in LDH at Day 140 was in favor of iptacopan (iptacopan vs. eculizumab: -9.061, p=0.0005; iptacopan vs. ravulizumab: ‑8.241, p=0.0013). The rate ratio in transfusion rate per patient-month was also in favor of iptacopan (iptacopan vs. eculizumab: 0.006, p=0.0004; iptacopan vs. ravulizumab: 0.008, p=0.0008).

CONCLUSIONS: These results suggest that iptacopan is more effective compared to eculizumab and ravulizumab in reducing LDH levels and rate of transfusions in C5i-naïve PNH patients and should be interpreted in the context of the ITC.

Conference/Value in Health Info

2024-11, ISPOR Europe 2024, Barcelona, Spain

Value in Health, Volume 27, Issue 12, S2 (December 2024)

Code

CO69

Topic

Clinical Outcomes

Topic Subcategory

Comparative Effectiveness or Efficacy

Disease

Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)

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