Paroxysmal Nocturnal Hemoglobinuria (PNH)

Understanding Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening blood disease that is associated with abnormally low (below normal) hemoglobin levels. PNH can appear at any age and in any race or gender, and is most often diagnosed in people in their early 30s.^1,2

Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue and difficulty breathing (dyspnea).

In PNH, blood cells lack complement regulatory proteins, so the body recognizes these healthy red blood cells as damaged.¹ This leads to uncontrolled activation of the complement cascade, initiated at C3, and results in the destruction of oxygen-carrying red blood cells (hemolysis).³ The complement cascade is a part of the immune system that is responsible for recognizing and eliminating pathogens and damaged cells in the blood.

Retrospective studies show that, even on eculizumab, approximately 70% of people with PNH have low hemoglobin levels,^4,5 and 36% require one or more transfusions a year.⁶

Pegcetacoplan (APL-2) in PNH

Pegcetacoplan is a targeted C3-inhibitor designed to regulate uncontrolled or excessive complement activation. With this approach, we believe that pegcetacoplan may have the potential to provide broad control of the red blood cell destruction (hemolysis) that drives the symptoms of PNH.

Resources

• National Organization for Rare Disorders (NORD)
• Aplastic Anemia & MDS International Foundation (AA&MMDSIF)
• Aplastic Anemia & Myelodysplasia Association of Canada (AAMAC)
• Canadian Association of PNH Patients
• Global Genes
• EURORDIS
• PNH Support

References

1. Paroxysmal nocturnal hemoglobinuria (PNH). The Sidney Kimmel Comprehensive Cancer Center Web site. https://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/paroxysmal_nocturnal_hemoglobinuria_PNH.html. Accessed November 20, 2019.
2. Besa EC. Paroxysmal nocturnal hemoglobinuria (PNH). MedScape 2017; https://emedicine.medscape.com/article/207468-overview. Accessed November 20, 2019.
3. Rosse WF, Ware RE. The molecular basis of paroxysmal nocturnal hemoglobinuria. Blood. 1995;86(9):3277-3286. Accessed November 20, 2019.
4. Risitano AM, Marotta S, Ricci P, et al. (2019) Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
5. Risitano AM, Notaro R, Marando L, et al. (2009) Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113(17):4094-4100.
6. McKinley CE, Richards SJ, Munir T, et al. Extravascular hemolysis due to C3-loading in patients with PNH treated with eculizumab: defining the clinical syndrome. Blood. 2017;130(Suppl 1):3471.

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