Longer-Term Treatment for Rare Blood Disorder Fares Well in Phase 3 Trial

Alexion announces positive top-line results for ALXN1210 in PNH

A new treatment for the rare blood disease paroxysmal nocturnal hemoglobinuria (PNH) that would cut the number of infusions needed each year by three-quarters fared well in a pivotal phase 3 study, the developer announced.

 ALXN1210 (Alexion Pharmaceuticals, Inc.), an investigational long-acting C5 complement inhibitor, demonstrated noninferiority to eculizumab (Soliris, Alexion) in complement inhibitor treatment-naïve patients with PNH based on the coprimary endpoints of transfusion avoidance and normalization of lactate dehydrogenase (LDH) levels, a direct marker of complement-mediated hemolysis in PNH.

The study also demonstrated noninferiority 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 (Hb) levels. In addition, numeric results for all six endpoints favored ALXN1210. There were no notable differences in the safety profiles for ALXN1210 and eculizumab.

For ALXN1210 versus eculizumab, transfusion avoidance was 73.6% versus 66.1%, LDH normalization was 53.6% versus 49.4%, change in LDH levels was –76.8%  versus –76.0%, improvement in FACIT scale was 7.1 versus 6.4, breakthrough hemolysis was 4.0% versus 10.7%, and stabilization of Hb levels was 68.0% versus 64.5%. The study also confirmed that ALXN1210 provides immediate and complete (more than 99%) inhibition of the complement C5 protein that is sustained over the entire eight-week dosing interval.

Alexion expects to make regulatory submissions of ALXN1210 in PNH in the U.S., European Union, and Japan in the second half of 2018.”

“Having a new treatment option that achieves transfusion avoidance, and provides rapid and sustained normalization of LDH levels when administered six times a year could be a meaningful improvement for patients with PNH who currently need 26 infusions per year,” said Jong Wook Lee, MD, Professor of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea, who is an investigator in the ALXN1210 study.

Detailed results from this study will be presented at a future medical congress.

This randomized, open-label, active-controlled, multinational, multicenter study evaluated the efficacy and safety of ALXN1210 compared to eculizumab administered by intravenous (IV) infusion to patients at least 18 years of age. The study enrolled 246 adults with a confirmed diagnosis of PNH who had never been treated with a complement inhibitor and presented with LDH levels of at least 1.5 times the upper limit of normal at the time of screening, as well as with PNH-related signs or symptoms within three months of screening. Patients in the ALXN1210 arm received a single loading dose of ALXN1210, followed by regular maintenance weight-based dosing every eight weeks. Patients in the eculizumab arm received four weekly induction doses, followed by regular maintenance dosing every two weeks. Both arms were treated for 26 weeks.

In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis, which in turn can result in progressive anemia, fatigue, dark urine, and shortness of breath. The most devastating consequence of chronic hemolysis is thrombosis, which can damage vital organs and cause premature death.

Source: Alexion; March 15, 2018.