Efficacy of Clinical Interventions in Paroxysmal Nocturnal Hemoglobinuria Patients Previously Treated With C5 Inhibitors: A Systematic Literature Review

Speaker(s)

Munro I1, Shodimu V1, Webb N2, Pannagl K3, Wiyani A4, Balp MM5
1Source Health Economics, London, UK, 2Source Health Economics, Oxford, OXF, UK, 3Novartis Pharmaceuticals UK Ltd, London, LON, UK, 4Novartis Pharmaceuticals UK Ltd, London, UK, 5Novartis Pharma AG, Basel, BS, Switzerland

Presentation Documents

OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood condition for which treatments include infusion complement 5 inhibitors (C5i; eculizumab; ravulizumab), C3i (pegcetacoplan), oral monotherapy Factor B inhibitor (iptacopan), and oral Factor D inhibitor (danicopan) combined with C5i. This systematic literature review (SLR) aimed to identify evidence on the clinical efficacy of iptacopan and comparators in adult PNH patients.

METHODS: The SLR was conducted following the Cochrane Handbook for Systematic Reviews of Interventions v6.3 and based on a PICOS framework. Searches were conducted in biomedical databases until April 19th, 2023, and via hand-search. Here we present outcomes from clinical trials (CTs) focusing on hemoglobin (Hb) and transfusion avoidance in C5i-experienced patients.

RESULTS: A total of 109 publications were included; among them, 45 reported on 16 CTs and four of these were in C5i-experienced patients (two Phase 3 [PEGASUS: pegcetacoplan vs. eculizumab and APPLY-PNH: iptacopan vs. C5i], and two Phase 2 single-arm trials [danicopan+eculizumab, and iptacopan+eculizumab]).

Primary endpoints were absolute change from baseline (CFB) in Hb at week 16 in PEGASUS and hematological response at week 24 (% patients with ≥2g/dL Hb increase; % patients with Hb ≥12g/dL) in APPLY-PNH. Secondary endpoints included transfusion avoidance (PEGASUS and APPLY-PNH).

Pegcetacoplan was superior to eculizumab with a mean difference in CFB in Hb of 3.84 g/dL (p<0.001) and % patients avoiding transfusions (85% vs 15%, p<0.001; treatment difference of 63% [95% CI: 48-77]). Iptacopan was superior to C5i with treatment differences for patients with ≥2 g/dL Hb increase: 80.2% (95% CI: 71.2-87.6; p<0.0001), Hb ≥12 g/dL: 67.0% (95% CI: 56.4-76.9; p<0.0001) and transfusion avoidance 68.9% (95% CI: 51.4-83.9; p<0.0001); iptacopan (94.8%) vs C5i (25.9%).

CONCLUSIONS: Iptacopan and pegcetacoplan showed superiority versus their comparators in the respective trials in C5i-experienced populations, but were not studied head-to-head, therefore an indirect treatment comparison is warranted.

Code

SA52

Topic

Study Approaches

Topic Subcategory

Literature Review & Synthesis

Disease

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