About PNH

• PNH is a rare, acquired clonal disorder of hematopoietic stem cells caused by a somatic mutation in the PIG-A gene, leading to the production of red blood cells with absent or decreased expression of GPI-anchored proteins, including CD55 and CD59^1-3

• In the absence of CD55 and CD59, RBCs become susceptible to complement mediated-hemolysis²

• Hemolysis can be intravascular or extravascular. IVH occurs inside the blood vessels, while EVH occurs in the liver and spleen²

• IVH occurs when PNH RBCs are destroyed by the membrane attack complex (MAC) in the terminal complement pathway^2,4

• EVH occurs when C3 fragments get deposited on PNH RBCs, tagging them for removal and destruction by macrophages in the liver or spleen in the proximal pathway of the complement system^2,4

A cross-sectional US survey of adults with self-reported diagnoses of PNH (N=122) evaluated the relationship between exposure to terminal complement inhibitors (eculizumab: n=35; ravulizumab: n=87) and clinical parameters, PNH symptoms, quality-of-life outcomes, and FACIT-Fatigue scores. Most patients (96.7%; eculizumab: n=35; ravulizumab: n=83) were on a C5i for ≥3 months.²

• History of aplastic anemia was reported in 33.6% (41/122) of patients

• Other comorbidities, such as myelodysplastic syndrome and other bone marrow disorders, were reported by <6% (n=7/122) of patients

Potential study limitations include:

• The sample size for this survey is small, given PNH is a rare disease

• The survey could be subject to selection bias, where dissatisfied patients are more motivated to participate

• Subjectivity of patient-reported outcomes

PNH can have a substantial impact on patients' day-to-day experiences