Soliris Demonstrates Reductions In Hemolysis, Improvements In Fatigue

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Soliris (eculizumab) therapy reduced hemolysis and improved fatigue, overall quality of life and anemia in a diverse population of patients with a rare blood disorder called paroxysmal nocturnal hemoglobinuria (PNH), according to an analysis of the Phase III SHEPHERD study published online in Blood, the journal of the American Society of Hematology.

Soliris, Hemolysis and PNH

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 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.(1-3)

Efficacy in a Broader Population

"The data from the SHEPHERD study confirm the earlier findings from the placebo-controlled TRIUMPH study," said Robert A. Brodsky, M.D., lead author of the SHEPHERD publication and Director, Division of Hematology and Associate Professor of Medicine and Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine. "The improvements in symptoms and signs of this debilitating disease were observed irrespective of baseline levels of hemolysis and degree of thrombocytopenia. Importantly, SHEPHERD encompassed a broad group of patients who are typical of the type of patients that are seen day to day in practice."

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SHEPHERD examined the safety and efficacy of eculizumab in a broader, more diverse population of PNH patients than the TRIUMPH study by allowing enrollment of patients with minimal transfusion requirements and/or evidence of thrombocytopenia to enter the trial. A total of 69 patients (71%) in the SHEPHERD study would not have met the inclusion criteria for entry into the companion Phase III double-blind placebo-controlled TRIUMPH trial.(4)

Clinical Data

The online publication in Blood, titled "Multicenter phase III study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria" reported data from the 97 patients, enrolled at 33 international sites, studied in the non-placebo controlled open-label Soliris Phase III SHEPHERD trial. The primary efficacy endpoint in this 52-week, open-label study was hemolysis, as measured by serum lactate dehydrogenase (LDH) levels. LDH is released during red blood cell destruction. Every patient treated with Soliris had a substantial reduction in hemolysis as measured by levels of LDH. LDH was reduced from a mean of 2201 plus or minus 105 U/L at baseline to 297 plus or minus 21 U/L at 52 weeks (P < 0.001).

"In addition to the universal improvement in hemolysis, patients in SHEPHERD experienced significant improvements in fatigue, overall quality of life, and anemia," said Leonard Bell, M.D., chief executive officer of Alexion. "For many patients, treatment with Soliris results in life-changing improvements in daily living. The beneficial impact of eculizumab on multiple aspects of patients' lives observed in both SHEPHERD and TRIUMPH reinforces Alexion's goal that every patient who can benefit from Soliris will have access to Soliris."

Fatigue, as measured by the FACIT-Fatigue instrument, significantly improved within one week of eculizumab treatment; this improvement was maintained throughout the 52 weeks of the study period (P < 0.001). The mean plus or minus SE change from baseline in FACIT-Fatigue score at 52 weeks was 12.2 plus or minus 1.1 (P < 0.001).

Quality of life assessments were also determined using the EORTC QLQ-C30 instrument. A significant improvement in fatigue scores was demonstrated on the EORTC QLQ-C30 fatigue scale by study week 1; this improvement was maintained at each study visit through week 52 (P < 0.001, mixed model analysis). Significant improvement in scores was shown with the instrument for global health status (P < 0.001), on all 5 scales for patient functioning (P < 0.001), on all 3 symptom scales (P less than or equal to 0.002), and on 4 of 6 single-item measures (P < 0.001).

Soliris treatment also led to an improvement in anemia. The increase in hemoglobin occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient during the year prior to the study to 0.0 units per patient during the 52 week study (P < 0.001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire study period. Improvements in hemolysis, fatigue, and transfusion requirements with Soliris were independent of baseline levels of hemolysis and degree of thrombocytopenia.

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