The phase III trial, named SHEPHERD, together with the already enrolling pivotal efficacy trial called TRIUMPH, comprise the phase III paroxysmal nocturnal hemoglobinuria (PNH) program which was agreed with the FDA under the special protocol assessment (SPA) process.
PNH is a blood disorder characterized by the onset of severe anemia, chronic fatigue and intermittent episodes of dark colored urine, known as hemoglobinuria. PNH patients are also at increased risk of forming life- threatening blood clots, or thromboses, which are a leading cause of death in this disease.
It is expected that, if successful, the trials will complete the application that will serve as the primary basis of review for the approval of a biologics license application (BLA) for eculizumab in the PNH indication.
A main objective of the SHEPHERD trial is to generate additional safety data with eculizumab in hemolytic PNH patients with a history of transfusion, and additional endpoints will include hemolysis and quality of life measures. The study is expected to enroll approximately 75 patients in the US, Canada, Europe and Australia. Results of six months of therapy are expected during the second half of 2005.
Alexion announced the initiation of treatment in the pivotal TRIUMPH phase III efficacy trial in November 2004. TRIUMPH is examining the effects of eculizumab on the co-primary endpoints of hemoglobin stabilization and blood transfusion in hemolytic, transfusion-dependent PNH patients during six months of therapy.
The SHEPHERD trial marks the third study performed with eculizumab in PNH patients. Results of the first trial were reported in the New England Journal of Medicine in February 2004.
Results showed that patients treated with eculizumab experienced a substantial decrease in the destruction of PNH red blood cells, as lactate dehydrogenase (LDH) levels fell from a mean of 3,111 international units per liter to 594 international units per liter, and the mean percentage of PNH red blood cells increased from 36.7% of the total red cell population to 59.2%.
If approved for PNH, eculizumab would represent the first of a new class of anti-inflammatory therapeutics-terminal complement inhibitors-as well as the first drug available specifically for patients suffering from this rare blood disease.
Currently, physicians prescribe either steroids or other immunosuppressive drug therapies to help patients cope with the symptoms of anemia, as no drugs are currently approved to specifically treat PNH.