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Many people in modern society suffer from chronic fatigue. However, if your fatigue becomes more severe than usual or persists for an extended period, it could indicate a rare condition called Paroxysmal Nocturnal Hemoglobinuria (PNH).
According to medical experts, PNH is a life-threatening rare blood disorder that affects approximately 1 to 1.5 people per million worldwide. It’s more prevalent in East Asian countries like South Korea, China, and Japan than in Western nations.
In South Korea, the number of patients nearly doubled from 260 in 2010 to 504 last year. While PNH can occur at any age, its frequency tends to increase. The median age of diagnosis is around 36.
The primary characteristic of PNH is hemolysis, in which red blood cells are destroyed, and hemoglobin is released into the bloodstream. This disruption in blood flow can lead to various life-threatening complications.
PNH occurs due to genetic deficiencies in red blood cells, causing hematopoietic stem cells to fail to protect against external attacks. This results in intravascular hemolysis (IVH) and extravascular hemolysis (EVH).
Professor Go Young Il of Seoul National University Hospital’s Hematology-Oncology Department explains that PNH causes anemia and chronic fatigue, significantly impacting patients’ quality of life. In severe cases, it can lead to thrombosis or bone marrow failure, potentially resulting in death.
He notes that PNH can be challenging to detect in its early stages due to the absence of distinct symptoms. While fatigue is common in today’s society, he advises seeking medical attention if you experience extreme tiredness or notice cola-colored urine.
Currently, the standard treatment for PNH involves C5 inhibitors. These drugs work by blocking the activation of the complement protein C5. While this treatment provides some control over hemolysis, it has limitations in fully addressing unmet needs.
C5 inhibitors only target the terminal part of the complement system as the disease progresses. As a result, while they can regulate intravascular hemolysis (IVH), they don’t entirely suppress extravascular hemolysis (EVH). This incomplete control of hemolysis poses ongoing challenges for PNH patients.
It’s particularly problematic when patients who don’t respond well to C5 inhibitors need to rely on blood transfusions. Up to 32% of patients may depend on transfusions due to persistent anemia, and as many as 89% continue to experience fatigue. This persistent fatigue is one of the most debilitating symptoms for patients.
C5 inhibitors also require intravenous administration every 2–8 weeks, with each session taking 240–330 minutes, including travel, injection, and recovery time.
In light of these challenges, a new drug (Iptacopan) that aims to address these unmet needs was approved in South Korea last August. It inhibits factor B within the complement system, offering a more comprehensive approach to controlling hemolysis.
Acting higher up in the alternative pathway regulates both IVH and EVH. Unlike C5 inhibitors, it impacts both C3 and C5, improving hemolysis across all areas.
Go explains, “While C5 inhibitors have been the standard treatment, their mechanism of action limits their ability to control extravascular hemolysis. Even with C5 inhibitor treatment, up to half of the patients may still require blood transfusions.”
He continues, “B-factor inhibitors have emerged as an alternative. Factor B operates at a higher level in the complement cascade than C5. By inhibiting factor B, we can comprehensively control both intravascular and extravascular hemolysis, which was previously challenging to manage.”
He also points out that while B-factor inhibitors have been approved in South Korea, they are not yet covered by insurance, limiting patient accessibility. He concludes, “While it offers a treatment option that addresses the unmet needs of the existing standard therapy, improving accessibility remains a critical issue to be resolved.”