Alexion Pharmaceuticals, Inc. has initiated the treatment phase in the phase III SHEPHERD trial, evaluating the investigational drug eculizumab in patients with the chronic orphan blood disorder Paroxysmal Nocturnal Hemoglobinuria (PNH).

The SHEPHERD trial, together with the already enrolling pivotal efficacy trial called TRIUMPH, comprise the phase III PNH programme which was agreed with the FDA under the Special Protocol Assessment (SPA) process. 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 haemolytic PNH patients with a history of transfusion. SHEPHERD is an open-label, non-placebo-controlled, multi-centre clinical trial. Additional endpoints will include haemolysis and quality of life measures. The study is expected to enrol approximately 75 patients in the US, Canada, Europe and Australia. Results of six months of therapy are expected during the second half of 2005. It is anticipated that patients will be followed for a second six-month period under the SHEPHERD protocol and then in an extension trial, according to the company release.

Previously, Alexion announced the initiation of treatment in the pivotal TRIUMPH Phase III efficacy trial in November 2004. TRIUMPH, which is a double-blind, randomized, placebo-controlled multi-centre clinical trial, 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 study is expected to enrol approximately 75 patients in the US, Canada, Europe and Australia and includes an observation phase for each patient prior to treatment. It is anticipated that patients will be followed in an extension trial following the completion of TRIUMPH.

"We are pleased to continue the rapid development of eculizumab in this important indication, first with the enrolment of patients into TRIUMPH, and now with the enrolment of additional patients into the companion SHEPHERD trial," said Leonard Bell, chief executive officer of Alexion. "With a focus on driving the PNH programme forward to meet the needs of the severely underserved PNH patient population, we will strive to complete enrolment and the initial six months of treatment in SHEPHERD, as well as the randomization and treatment of patients in TRIUMPH, in 2005. We believe that, if successful, the TRIUMPH pivotal trial, together with results from SHEPHERD, should provide a solid basis to support licensing applications for the PNH indication in the US and Europe," he added.

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. In December 2003, Alexion had received orphan drug status for the use of eculizumab in PNH from both the FDA and the European Agency for the Evaluation of Medicinal Products, the release added.

PNH is a blood disorder characterized by the onset of severe anaemia, chronic fatigue and intermittent episodes of dark coloured 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 (approximately 50%) in this disease.

Alexion is engaged in the discovery and development of therapeutic products aimed at treating patients with a wide array of severe disease states, including hematologic and cardiovascular disorders, autoimmune diseases and cancer.