Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is a rare, acquired, clonal disorder of hematopoietic stem cells that is characterized by hemolysis, bone marrow failure, and thrombosis^1,2

• PNH develops due to a mutation in PIGA, which is necessary for the creation of GPI anchors on the cell surface that attach proteins, including CD55 and CD59^1,3,4
• CD55 and CD59 normally prevent the complement system from destroying normal cells, and in PNH, loss of the GPI anchor results in the lack of CD55 and CD59 on cells^1,4-6
• This leads to complement-mediated hemolysis^1,4

The complement system features 3 pathways made up of a large number of distinct plasma proteins that react with one another to help fight infection. Each pathway is triggered differently but ultimately leads to cell destruction⁴

Epidemiology

US incidence rate of PNH⁸
≈ 6 cases per 1 million person-years

US prevalence of PNH⁸
12 to 13 per 1 million individuals

PNH affects adults irrespective of age or sex^2,8

• Median age at onset is ~36 years
• PNH rarely occurs in children

The Burden of PNH²

Key signs and symptoms

• Anemia (median hemoglobin level, 9.8 g/dL)
• Thrombosis
  • Thrombotic events are the leading cause of mortality in PNH, accounting for ≤67% of deaths with a known cause
  • 13% of patients have a history of thrombotic events
• Hemoglobinuria (45%)
• Fatigue (81%)
• Abdominal Pain (35%)

These symptoms can have a substantial impact on quality of life, hospitalization and employment.

Unmet Medical Needs in PNH

Diagnosing PNH⁹
Flow cytometry is the gold-standard test to diagnose PNH; however, late diagnosis and delayed treatment remain barriers due to the rarity of PNH and numerous symptoms that overlap with other disorders

Due to the multifactorial symptoms of PNH, diagnosis can be challenging, often characterized by a lengthy and complex patient experience⁹

Approximately one-third of patients on standard of care fail to achieve hemoglobin stabilization (defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion)¹⁰

Twenty-six percent to 34% of patients on standard of care require chronic RBC transfusions which can lead to transfusion dependence and complications such as iron overload^10-12

In paroxysmal nocturnal hemoglobinuria, dysregulation of the complement system leads to complement-mediated hemolysis.^13-15