Alexion Pharmaceuticals Inc. achieved positive results in its pivotal phase III placebo-controlled randomised efficacy trial using eculizumab in Paroxysmal Nocturnal Haemoglobinuria (PNH) patients. All pre-specified primary and secondary endpoints in the international trial were achieved with statistical significance. The pre-specified, co-primary endpoints were median transfusion rate and haemoglobin stabilisation over six months. The study enrolled 87 patients at 45 sites in the US, Canada, Europe and Australia.

PNH, a rare form of haemolytic anaemia, is an acquired genetic blood disorder characterised by destruction of red blood cells by the body's complement system (a component of the immune system). Patients with PNH lack naturally-occurring complement inhibitors which prevent red blood cell destruction. Eculizumab, a long-acting C5 terminal complement inhibitor, is a monoclonal antibody drug that selectively blocks terminal complement activation. There currently is no therapy specifically available for treatment of PNH.

"The TRIUMPH study represents an important milestone in the development of eculizumab for PNH and, hopefully, for the patients afflicted with this chronic, severely debilitating, and life-threatening disease," said Dr. Peter Hillmen, lead investigator and chairman of the TRIUMPH steering committee, and Consultant Haematologist of the General Infirmary at Leeds, Leeds, UK.

"Treatment options are extremely limited for PNH and at present there is no approved therapy. Eculizumab is currently the only potential therapy that addresses haemolysis and the associated morbidities in PNH. In the trial, eculizumab arrested the chronic intravascular haemolysis that is due to the genetic deficiency of natural complement inhibitors on PNH red blood cells a hallmark and underlying cause of PNH's haemolytic anaemia. Many TRIUMPH patients on the eculizumab regimen were able to resume normal activities of daily living after having experienced years of debility. I believe that these results strongly support the potential for eculizumab to markedly improve the lives of patients with PNH," added Hillmen.

All of the pre-specified secondary endpoints in TRIUMPH, including reduction in lactate dehydrogenase (LDH), quality of life as measured by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) instrument, and transfusion avoidance, were also achieved with statistical significance. Additionally, eculizumab appeared to be well tolerated with an adverse event profile comparable to placebo. The most frequent adverse events with eculizumab were headache, nasopharyngitis and back pain.

"The compelling results observed with eculizumab in the PNH TRIUMPH efficacy study represent an important accomplishment in the evolution of Alexion toward a commercial entity. As we continue the ongoing SHEPHERD study, we are focused on preparations to meet with US and European regulatory agencies. We are currently targeting submission of marketing applications for eculizumab in PNH during the second half of this year," said Leonard Bell, chief executive officer of Alexion.

Alexion previously reached an agreement with the FDA on the design of TRIUMPH, a pivotal phase III efficacy trial with eculizumab in PNH patients, and the companion phase III SHEPHERD trial, under the FDA's Special Protocol Assessment (SPA) process. SHEPHERD is an open-label, non-placebo-controlled, multi-centre clinical trial primarily aimed at generating safety data with eculizumab in a broader population of hemolytic PNH patients. Efficacy measures will also be obtained in the study. The SHEPHERD protocol includes 12 months of treatment with a six-month interim analysis. It is expected that data from these trials will serve as the primary basis of review for the approval of a biologics license application (BLA) for eculizumab in the PNH indication, as well as the basis of review for a European marketing authorisation application (MAA). Eculizumab has been granted orphan drug status from both the US and European regulatory agencies to treat PNH.

Alexion discovers and develops therapeutic products aimed at treating patients with a wide array of severe disease states, including haematologic and cardiovascular disorders, autoimmune diseases and cancer.