Alexion Pharmaceuticals, Inc. announced the publication of its eculizumab clinical trial results in patients with paroxysmal nocturnal hemoglobinuria (PNH) in The New England Journal of Medicine. In the three-month open label trial involving 11 transfusion-dependent patients all receiving eculizumab, notable reductions in red blood cell destruction, hemoglobinuria and blood transfusions were achieved. Patients also reported an improvement in quality of life after initiating eculizumab therapy. Eculizumab, an investigational drug therapy being developed by Alexion, has been granted Orphan Drug Status from both the US and European regulatory agencies to treat PNH. The company is in discussions with the US Food and Drug Administration to complete the design of a pivotal Phase III programme.

PNH is a blood disorder characterized by the onset of severe anemia, chronic fatigue and intermittent episodes of black-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 per cent) in this disease. People with PNH have an acquired deficiency of proteins that normally protect red blood cells from a component of the body's natural defense system, known as the complement cascade. The lack of these complement inhibitor proteins leaves the PNH red blood cells susceptible to destruction (hemolysis), which can cause patients to become anemic and, in some cases, dependent on blood transfusions. Currently, physicians prescribe either steroids or other immunosuppressive drug therapy to help patients cope with the symptoms of anemia, as no drugs are currently approved to specifically treat PNH. Estimates suggest that up to 10,000 people in the US suffer from this condition.

"The eculizumab trial is the first clinical study to demonstrate a statistically significant reduction in hemolysis and blood transfusions in PNH patients," said the manuscript's lead author and the study's principal investigator, Peter Hillmen, consultant hematologist of The General Infirmary at Leeds, Leeds, United Kingdom. "We were particularly encouraged by the observation in the study that the drug appeared to increase the survival of PNH red blood cells over the duration of the trial, which highlights the importance of the role of terminal complement inhibition in PNH. This supports the potential of a role for eculizumab in managing this disease."

In this study, patients received infusions of eculizumab, a recombinant humanized monoclonal antibody designed to block complement protein C5. The drug was given weekly for five weeks and then every other week for a total of 12 weeks. The trial was designed to investigate whether the antibody could reduce intravascular hemolysis, episodes of hemoglobinuria and transfusion requirements in these patients. Results of the study showed that patients experienced a substantial decrease in the destruction of red blood cells, as lactate dehydrogenase (LDH) levels fell from 3,111 IU per liter to 594 IU per liter. The mean percentage of PNH red blood cells increased from 36.7 per cent of the total population found in the body to 59.2 per cent, which helped reduce the mean patient transfusion rates from 2.1 units per patient, per month, to 0.6 units per patient, per month. Episodes of hemoglobinuria were reduced by 96 per cent and quality of life measurements, using a standard instrument called EORTC QLQ C-30, a questionnaire developed to assess quality of life in cancer patients particularly suffering from severe fatigue and anemia, substantially improved during the trial. In this trial, eculizumab appeared safe and well tolerated, and in no cases were antibodies against the drug detected. Adverse events were similar in type and frequency to those reported with eculizumab or placebo in other controlled trials. The most common adverse events were headache, upper respiratory infection, muscle/joint aches, and influenza-like symptoms, and the severe adverse events were viral chest infection, dizziness and shivering.

"We are very encouraged by the clinical results from this study, and will look to further confirm them in a larger, pivotal program later this year," said Leonard Bell, chief executive officer of Alexion Pharmaceuticals, Inc. "For patients suffering from a life-long hemolytic disease such as PNH, the reductions in hemolysis and transfusions, and the improved quality of life with eculizumab treatment show promise. We are especially pleased to announce that we will also be partnering with the International PNH Interest Group to launch a global PNH patient registry, which will serve to help the medical and broader PNH community understand better the natural history of PNH, develop best practice treatment guidelines and improve patient outcomes for this devastating disease."