IPTACOPAN ASH UPDATE
Complement regulation in PNH is impaired 1,2
Alternative pathway
(Tick-over)
C3
Factor B
C3(H2O)
Factor D
CD55
C3 convertase
Factor B
Factor D
C3
CD55
C3b
C3
convertase
C3a
C3b
Proximal pathways
Terminal pathway
C5
convertase
C5 inhibitors
C5
C6, C7,
C8, C9
C5a
C5b
Extravascular hemolysis
via C3 opsonization and
phagocytosis
CD59
MAC
Intravascular
hemolysis
→ PNH is a rare, chronic hematological disorder
characterized by intravascular hemolysis (IVH),
thrombophilia and bone marrow failure 1,2
→ Caused by an acquired mutation in hematopoietic
stem cells, which results in a lack of complement-
regulatory proteins, leading to IVH
→ Targeting the terminal complement pathway
at C5 can address IVH, reduce thrombosis and
improve overall survival 3-9
→ However, up to 2/3 of patients have clinically
meaningful residual anemia, largely because
of emerging extravascular hemolysis 1,10
C = complement component; CD = cluster of differentiation; GPI = glycosylphosphatidylinositol; MAC = membrane attack complex; PNH = paroxysmal nocturnal hemoglobinuria; SoC = standard of care. 1. Risitano AM et al. Front Immunol
2019;10:1157. 2. Risitano AM, Peffault de Latour R. Br J Haematol 2022;196:288-303. 3. Hillmen P et al. N Engl J Med 2006;355:1233-43. 4. Kelly RJ et al. Blood 2011;117:6786-92. 5. Brodsky RA et al. Blood 2008;111:1840-7.
6. Hillmen P et al. Blood 2007;110:4123-8. 7. Loschi M et al. Am J Hematol 2016; 91:266-70. 8. Kulasekararaj AG et al. Blood 2019;133:540-9. 9. Lee JW et al. Blood 2019;133:530-9.
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IPTACOPAN ASH UPDATE | DECEMBER 13, 2022
10. Risitano AM et al. Blood 2009;113:4094-100
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