Pivotal Phase III study of ALXN 1210 shows non-inferiority in paroxysmal nocturnal hemoglobinuria.- Alexion Pharma.

Alexion Pharmaceuticals announced that the pivotal Phase III study of ALXN 1210 demonstrated non-inferiority to Soliris (eculizumab) in complement inhibitor treatment-na�ve patients with paroxysmal nocturnal hemoglobinuria (PNH) based on the co-primary endpoints of transfusion avoidance and normalization of lactate dehydrogenase (LDH) levels, a direct marker of complement-mediated hemolysis in PNH. The study also demonstrated non-inferiority on all four key secondary endpoints: percentage change from baseline in LDH levels, change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, proportion of patients with breakthrough hemolysis, and proportion of patients with stabilized hemoglobin levels. In addition, numeric results for all six endpoints favored ALXN1210. There were no notable differences in the safety profiles for ALXN 1210 and Soliris.

Since non-inferiority was achieved across both co-primary and all four key secondary endpoints, the protocol allowed for superiority testing. The hierarchical testing order pre-specified breakthrough hemolysis as the first endpoint tested for superiority. Although ALXN 1210 did not achieve superiority, a numeric trend in favor of ALXN1210 was observed for breakthrough hemolysis (4.0% [0.6%,7.4%] vs. 10.7% [5.2%,16.3%] for Soliris) with a p-value of 0.074. The study also confirmed that ALXN 1210 provides immediate and complete (more than 99%) inhibition of the complement C5 protein that is sustained over the entire 8 week dosing interval. Additionally, treatment with ALXN 1210 reduced mean LDH levels to approximately the upper limit of normal (1.0-1.1 times ULN) between months one and six.

ALXN 1210 was generally well tolerated with a safety profile that is consistent with that seen for Soliris. The most frequently observed adverse event was headache. The most frequently observed serious adverse event was pyrexia. One patient in the Soliris arm died from lung cancer (unrelated to Soliris treatment) during the extension phase of the study. Two patients withdrew from the Soliris arm for reasons unrelated to treatment.