PNH Patients With Lower Levels Of Hemolysis Have Significant Disease Burden

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Paroxysmal Nocturnal Hemoglobinuria

Soliris (eculizumab) therapy reduced hemolysis, fatigue, thromboses (blood clots) and transfusion requirements in patients with a rare blood disorder called paroxysmal nocturnal hemoglobinuria (PNH), including those who might have been expected to have less severe disease, according to data from an ongoing open-label clinical study presented today at the 49th Annual Meeting of the American Society of Hematology Meeting in Atlanta.

The data were highlighted in an oral presentation titled, "High Incidence of Progression to Significant Disease Burden in Paroxysmal Nocturnal Hemoglobinuria Patients with Lower Levels of Hemolysis, Mild Anemia and Minimal Transfusion: Clinical Improvement with Eculizumab Therapy."

In the study, (1) Soliris was associated with significant long-term clinical improvements in patients with PNH, regardless of baseline degree of hemolysis, anemia or transfusion requirements. The study also demonstrated that patients who might have been expected to have less severe disease, considering their baseline clinical characteristics, suffered from significant disease burden.

"PNH patients once thought to have less severe disease based on their clinical characteristics actually face significant disease burden from anemia, fatigue, impaired quality of life, blood transfusion requirements and blood clot risk," said Monica Bessler, MD, PhD, lead author of the study and Professor of Medicine, Professor of Pharmacology and Molecular Biology, Washington University in St. Louis School of Medicine. "The results presented today show that, in this study group, regardless of disease severity, long- term Soliris treatment provides important clinical improvements in their disease signs, symptoms and complications."

"We continue to observe that the PNH patient population includes a wide range of patients with a broad clinical profile," said Leonard Bell, MD, Chief Executive Officer of Alexion Pharmaceuticals. "The results presented today provide further evidence for the utility of Soliris therapy in patients with diverse manifestations of PNH. We remain committed to our goal that all patients who can benefit from Soliris will have access to it."

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Soliris, developed by Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN), is the first therapy approved for the treatment of patients with PNH, a rare, debilitating and life-threatening blood disorder defined by the destruction of red blood cells, or hemolysis. Soliris is a complement inhibitor indicated for the treatment of patients with PNH to reduce hemolysis. In patients with PNH, hemolysis can cause thromboses, kidney disease, liver dysfunction, disabling fatigue, impaired quality of life, recurrent pain, shortness of breath, pulmonary hypertension, intermittent episodes of dark colored urine (hemoglobinuria), and anemia. (2-4)

Clinical Data

In the ongoing open-label clinical study, investigators examined the long- term clinical effect of Soliris in patient subgroups, including those with lower levels of hemolysis, mild anemia and minimal transfusion requirements.

Data were analyzed by levels of baseline hemolysis (as indicated by baseline quartiles of lactate dehydrogenase, LDH), anemia (Hgb < 10.5 g/L vs greater than or equal to 10.5 g/L), and transfusion requirements (transfusion episodes in prior year greater than 1 vs 1 or 0 episodes). Hemolysis, fatigue and transfusion requirements were examined using a ranking test to measure efficacy during both the first and the most recent six months of Soliris therapy; patients received a median of 22 months of treatment.

Hemolysis was significantly reduced with eculizumab treatment in patients with all levels of baseline hemolysis. In patients with the lowest quartile of hemolysis (< 1490 U/L), LDH was reduced from 1077 +/- 42 U/L pre-eculizumab to 323 +/- 22 U/L during the first six months and to 347 +/- 47 U/L during the most recent six months of Soliris therapy (P<0.001 for each comparison to baseline). Hemolysis was also significantly reduced during both the first and most recent six months of Soliris therapy in patients with mild anemia (Hgb of greater than or equal to 10.5 g/L) and minimal transfusion support prior to treatment (0 or 1 transfusion episode in the previous year) (P<0.001 for all subgroups at both time intervals).

In the study, patients who might have been considered to have less severe disease were found to have an elevated risk of blood clots prior to therapy and experienced the following reductions in the incidence of blood clots during Soliris therapy: for patients with the lowest quartile of baseline hemolysis, the rate decreased from 10.8 to 4.5 events per 100 patient years (P=0.009, n=48), for those with mild anemia from 5.2 to 0.8 events per 100 patient years (P<0.001, n=55), and for those with minimal pretreatment transfusion support from 4.9 to 0.0 events per 100 patient years (P=0.063, n=22).

Soliris treatment was associated with significant improvements in fatigue (as measured by the FACIT-Fatigue instrument), regardless of the baseline level of hemolysis, anemia, or pretreatment transfusion requirements. At baseline, patients who had the lowest levels of hemolysis, mild anemia, or minimal transfusion requirements reported fatigue. With patients in the lowest quartile of baseline hemolysis, FACIT-Fatigue scores improved by 6 points during the first six months and by 8 points during the most recent six months of Soliris therapy (P<0.001 for each comparison to baseline); an increase of 3 or more points is considered clinically meaningful in this instrument. (5) In patients with mild baseline anemia, fatigue scores improved by 5 points during the first six months and by 6 points during the most recent six months of therapy (P<0.001 for each comparison to baseline). Even in patients with minimal transfusion support prior to Soliris therapy, fatigue scores improved by 9 points during the first six months and by 15.5 points during the most recent six months of treatment (P<0.001 for each comparison to baseline).

In addition, in patients with history of bone marrow failure, units transfused were reduced from mean 9.2 +/- 1.2 units per patient prior to treatment to 4.4 +/- 1.4 units per patient during the most recent six months of Soliris treatment (P<0.001).

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