Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced the presentation of an analysis from the National Data Registry in South Korea that evaluated the association between hemolysis and mortality in patients with paroxysmal nocturnal hemoglobinuria (PNH). Researchers also presented new data from the PNH Registry, a multi-center, multi-national, observational study of patients with PNH: one presentation examined patient-reported quality of life, hospitalizations, and missed work, while a second evaluated the incidence of blood transfusions in patients with and without bone marrow disorders (BMD). Researchers reported these results at the 52nd American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando.
“Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective”
PNH is an ultra-rare, life-threatening blood disorder in which chronic uncontrolled activation of the complement system causes the chronic destruction of red blood cells (hemolysis). Alexion is the maker of Soliris® (eculizumab), a first-in-class terminal complement inhibitor that is the first treatment developed specifically for PNH.
Elevated Hemolysis Associated With Early Mortality and Risk of Thrombosis
Researchers presented a poster titled, "Association Between Elevated Hemolysis at Diagnosis and Early Mortality and Risk of Thrombosis In Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients with Cytopenia." The analysis, which included 301 PNH patients from the National Data Registry in South Korea, evaluated the presence of hemolysis and cytopenia at the time of diagnosis and subsequent patient outcomes.
Researchers concluded that PNH patients with hemolysis are at an increased risk of mortality and life-threatening complications, and that hemolysis is a potential risk factor for mortality and life-threatening complications independent of the presence of cytopenia. In PNH patients with elevated hemolysis, as measured by lactate dehydrogenase (LDH) levels, researchers reported significantly higher rates of mortality (16% vs. 4%;>
"This research provides further evidence that uncontrolled complement activation and the resulting chronic hemolysis are the underlying causes of the morbidities and mortality associated with PNH," said Leonard Bell, M.D., Chief Executive Officer of Alexion.
The PNH Registry: Burden of Disease from Patient Perspective
In a poster session on Saturday titled, "Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective," researchers presented patient-reported quality-of-life, hospitalization, and missed work outcomes for 431 patients enrolled in the PNH Registry. Patients were from 102 clinical sites in 17 countries and had completed a baseline questionnaire.
In the study, patients with PNH reported a reduced quality of life as measured by the EORTC QLQ-30 questionnaire, with a mean reduction of six to 12 points compared to the general population in five of the six EORTC function subscales: global health, physical functioning, role functioning, cognitive functioning, and social functioning. A change of five or more points on this scale is considered a clinically meaningful difference.
Patients with PNH also reported a substantially more severe level of fatigue as measured by the FACIT-Fatigue scale, with a 7.3 point reduction compared to the general population. A change of three or more points on this scale is considered a clinically meaningful difference.
In the six months before enrolling in the study, one in four patients (26%) were hospitalized, and one in three patients with a paid job (33%) missed work due to PNH. At least one in six patients (16%) reported not working or worked less due to PNH. Patients with a history of thrombosis had an increased risk of hospitalization, being unemployed, or working less. Patients who reported abdominal pain, dyspnea, or icterus had an increased risk of hospitalization, missed work, or being unemployed (all p<.05).
"Just a decade ago, we knew very little about PNH. Today, with the growing PNH Registry, we're amassing valuable data that help us better understand and manage patients with this disease," said Petra Muus, M.D., Ph.D., PNH Registry investigator and associate professor of hematology at the Radboud University Nijmegen Medical Center, Nijmegen, Netherlands. "We now have a more complete and quantitative picture of the debilitating nature of PNH and how it affects patients' abilities to lead healthy, productive lives."
The PNH Registry: Blood Transfusions in PNH Patients with and without Aplastic Anemia
A second set of PNH Registry data were presented in a poster session yesterday titled, "Use of Blood Transfusion in Paroxysmal Nocturnal Hemoglobinuria Patients with and without Aplastic Anemia in the Global PNH Registry." The study aimed to characterize the use of transfusions among PNH patients with and without underlying history of aplastic anemia (AA), a type of BMD.
The registry data indicate that patients with AA have a similar likelihood of elevated hemolysis - which drives the life-threatening complications of PNH - as do patients without BMD. At enrollment, 31.8% of PNH patients had a history of AA, while 49.2% had no history of BMD.
For patients with clone sizes <10%, 10-49%, and >50%, LDH multiples of upper limit of normal for AA and no BMD patients were 0.90 and 1.01, 1.55 and 2.00, and 4.70 and 4.96, respectively.
In addition, as compared to PNH patients without AA, patients with PNH and a history of AA reported similar frequency of abdominal pain and fatigue, more bruising and bleeding, and less dysphagia and hemoglobinuria. The analysis showed that approximately 40% of patients did not require a transfusion in the year prior to enrollment, regardless of AA history.
"These data add to the growing body of knowledge we're gaining through the PNH Registry, which already has made significant strides in helping us define PNH treatment objectives and best practices," said Hubert Schrezenmeier, M.D., Institute of Transfusion Medicine and Immunogenetics, Red Cross Blood Transfusion Services, Baden-Württemberg-Hessen, Ulm, Germany. "By joining the Registry, patients and physicians can help create a more robust set of data to improve the diagnosis and treatment of this rare, life-threatening disease."
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