ALXN1210 has demonstrated non-inferiority to eculizumab in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria, according to results from a pivotal Phase 3 study.
ALXN1210 has demonstrated non-inferiority to eculizumab (Soliris) in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH), according to results from a pivotal Phase 3 study.
The results were announced this morning by Alexion Pharmaceuticals, Inc., and were 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 Phase 3, randomized, open-label, active-controlled, multinational, and multicenter study evaluated the efficacy and safety of ALXN1210 administered by intravenous (IV) infusion to adult patients aged 18 years and older. Results were compared to that in patients administered eculizumab, the first and only treatment to be approved by the U.S. Food and Drug Administration (FDA) to reduce hemolysis in patients with PNH.
“We are very pleased with these positive data for ALXN1210 in the first and only head-to-head study versus Soliris, and the results reinforce our ambition to establish ALXN1210 as the new standard of care for patients with PNH. The data are also consistent with our hypothesis that immediate, complete, and sustained C5 inhibition is critical for patients with this potentially life-threatening disease,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion in a conference call this morning.
246 patients with a confirmed PNH diagnosis who had never been treated with a complement inhibitor were enrolled, and all participants had presented with LDH levels ≥ 1.5 times the upper limit of normal (ULN) at the time of screening, as well one or more of the PNH-related symptoms within 3 months of screening.
Also demonstrated in the study was non-inferiority across four significant secondary endpoints including: percentage change from baseline in LDH levels, change from baseline in LDH levels, change from baseline in quality of life (QOL) 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.
Breakthrough hemolysis was tested for superiority because non-inferiority was achieved across co-primary and all four secondary endpoints, and while ALXN1210 did not achieve superiority, a numeric trend in favor of the drug was observed.
“Having a new treatment option that achieves transfusion avoidance, and provides rapid and sustained normalization of LDH levels when administered 6 times a year could be a meaningful improvement for patients with PNH who currently need 26 infusions per year,” said Jong Wook Lee, M.D., Professor of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea, and an investigator in the ALXN1210 study in a press release.
ALXN1210 demonstrated tolerability and safety profile consistent to what historical data have reported for eculizumab. The most common adverse event (AE) was headache, and the severe AE most frequently observed was pyrexia, or increased body temperature.
All patients have been enrolled in an extension study of up to 2 years, during which they will receive ALXN1210 every 8 weeks, and Alexion intends to present detailed results from this Phase 3 study at a future medical conference.