Alexion is developing eculizumab and additional new therapeutics in hematology/cancer indications. In January of 2003, Alexion completed a three month pilot clinical trial in hemolytic transfusion-dependent PNH patients.

Clinical Results in Paroxysmal Nocturnal Hemoglobinuria

In July 2005 we announced that we completed randomization of patients of the pivotal Phase III TRIUMPH efficacy trial of eculizumab in patients with PNH. In accordance with the trial's design, enrolled patients first entered an observation phase of approximately three months to confirm their eligibility to be included in the trial, and then were randomized to receive either eculizumab or placebo in a six month treatment phase. TRIUMPH is a double-blind, randomized, placebo-controlled multi-center pivotal Phase III trial, examining the effects of eculizumab on the co-primary endpoints of hemoglobin stabilization and blood transfusion requirement in hemolytic, transfusiondependent PNH patients during six months of therapy. The study has enrolled patients in the U.S., Canada, Europe, and Australia. Approximately 85 PNH patients were randomized into the six month treatment phase, which exceeds the patient requirements agreed upon with the FDA as part of the SPA for TRIUMPH.

The TRIUMPH trial is our second study of eculizumab in PNH patients. Results of the first trial, a three month, open-label study in 11 patients, reported in the February 5, 2004 issue of the New England Journal of Medicine were that patients treated with eculizumab experienced a substantial decrease in the destruction of PNH red blood cells, with the mean percentage of these cells increasing from 36.7 percent of the total population found in the body to 59.2 percent (P=0.005), and lactate dehydrogenase levels, a biochemical marker of red blood cell destruction, falling from a mean of 3,111 IU per liter to a mean of 594 IU per liter (P=0.002). This reduction in PNH red blood cell destruction helped reduce the median patient transfusion rates from 1.8 units per patient, per month, to 0.0 units per patient, per month (P=0.003). Episodes of hemoglobinuria were reduced by an average of 96 percent (P>0.001) and quality of life measurements, using EORTC QLQ C-30, a standard questionnaire developed to assess quality of life in cancer patients particularly suffering from severe fatigue and anemia, substantially improved during treatment. In this trial, eculizumab appeared reasonably well tolerated, and antibodies against the drug were not detected. Adverse events reported for eculizumab or placebo were similar in type and frequency to those reported 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. In the June 2005 issue of the journal Blood, we reported on the safety and sustained effects of eculizumab in a 52-week extension of our pilot open-label PNH trial in these 11 patients. In this study, patients who received eculizumab continued to tolerate the drug reasonably well and experienced reduced hemolysis resulting in an increase in PNH red blood cells, a reduction in the need for transfusion, and improvements in multiple quality of life measures. Reported adverse events occurring in three or more patients were flu-like symptoms, sore throat, pain, nausea, bruising, cough, and upper respiratory infection. The adverse event profile for eculizumab-treated patients in this study is similar to that of placebo-treated patients in other patient population trials of eculizumab.

We have also completed enrollment in SHEPHERD, an open-label safety trial which will be primarily aimed at generating additional safety data with eculizumab in approximately 95 PNH patients in the United States, Canada, Europe, and Australia. The SHEPHERD protocol includes twelve months of treatment with a six month interim analysis. It is expected that, if successful, these two studies will complete the filing package that will serve as the primary basis of review for the approval of a Biologics License Application, or BLA, for the PNH indication. We also continue to enroll patients that have completed the TRIUMPH and SHEPHERD trials, as well as patients that have completed the Phase I clinical trial in an open-label extension trial to further evaluate safety data in eculizumab. We retain all rights to eculizumab in all indications worldwide.