Eculizumab (Soliris) cuts blood clot risk in rare blood disorder PNH: Alexion

Eculizumab, marketed under the brand name Soliris lowers the blood clotting and improves the quality of life in patients with a rare form of blood disorder called paroxysmal nocturnal hemoglobinuria (PNH), according to Alexion Pharmaceuticals, maker of the drug.

New data generated from 44 PNH patients with no history of prior blood transfusions, found that eculizumab (Soliris) increased intravascular hemolysis (red blood cell destruction), 87% reported impaired quality of life, and 28% had a history of clinically evident thrombosis (blood clots).

This group of patients from France, Italy, the Netherlands, Australia and the United States ranged in age from 16 to 84 years and in duration of diagnosis from 1 month to 30 years (average 3.8 years).

Prior to Soliris therapy, these never-transfused patients overall demonstrated increased intravascular hemolysis, as measured by elevated LDH. Quality of life was assessed by a healthcare provider and assessments included good (no impairment), or impairment which was further characterized with any of the following terms: mild impairment, disabling or moderate fatigue, disabling abdominal pain, shortness of breath with exertion, or poor quality of life.

Patients received 600 mg of Soliris every 7 days for 4 doses; followed by 900 mg one week later; then 900 mg every 14 days  for a median duration of 1.2 years.

All patients who received Soliris experienced a reduction in hemolysis following treatment, as measured by a median reduction in LDH from 1,603 U/L before treatment to 380 U/L after treatment.

Among 11 patients who received a quality of life assessment both before and after treatment, 91% reported an impaired quality of prior to treatment, compared with none following Soliris therapy.

Further, there was no reported thrombosis during treatment with eculizumab (11 patients with history of thrombosis) and the thrombosis event rate was significantly reduced from 7.85 to 0.

Eculizumab (Soliris), which is a terminal complement inhibitor, significantly reduced red blood cell destruction in all patients assessed in this retrospective study.

91% of patients with quality of life assessments both before and during Soliris treatment showed improvement in their quality of life during Soliris treatment. A significant reduction in clinically evident thrombosis, from 7.85 events per 100 patient years to zero events following Soliris treatment, was also observed.

“This study shows both the central role of unregulated complement activity and chronic hemolysis in PNH, and the significant clinical benefits of Soliris in all patients with PNH, regardless of pre-treatment transfusion status or hemoglobin levels,” stated Leonard Bell, M.D., Ph.D. Chief Executive Officer of Alexion.

Soliris has been approved by the U.S. Food and Drug Administration in March 2007, the European Commission in June 2007, Health Canada in January 2009 and Australia’s Therapeutic Goods Administration in February 2009 as the first treatment for all patients with PNH, an ultra-rare, debilitating and life-threatening blood disorder defined by chronic hemolysis, or the destruction of red blood cells.

Prior to these approvals, there were no therapies specifically available for the treatment of PNH.

Alexion presented the data at the 51st Annual Meeting of the American Society of Hematology (ASH) in a poster titled, “Clinical Impact of Unregulated Terminal Complement Activity in Never-Transfused Patients with Paroxysmal Nocturnal Hemoglobinuria.”

What is paroxysmal nocturnal hemoglobinuria (PNH)?

Patients with PNH suffer from hemolysis (red blood cell destruction) which leads to thromboses (blood clots), disabling fatigue, anemia, impaired quality of life, pulmonary hypertension, shortness of breath, recurrent pain, kidney disease and intermittent episodes of dark-colored urine (hemoglobinuria).

PNH is an ultra-rare blood disorder that strikes people of all ages, with an average age of onset in the early 30s. Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger.

PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.

Approximately one-third of patients with PNH do not survive more than five years from the time of diagnosis, it is estimated.

Kidney disease accounts for 18 percent of deaths among Japanese patients with PNH. PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS). In patients with thrombosis of unknown origin, PNH may be an underlying cause.

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery, development and commercialization of therapeutic products aimed at treating patients with a wide array of severe disease states, including hematologic and kidney diseases, transplant, cancer, and autoimmune disorders.Soliris is Alexion’s first marketed product.