BLA Submitted for ALXN1210 as Treatment for Patients with Ultra-Rare PNH

Alexion Pharmaceuticals, Inc. has submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for approval of ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare, potentially deadly disease of the blood.

“This first regulatory submission is an important step toward our goal of establishing ALXN1210 as the new standard of care for patients with PNH, building on 10 years of proven efficacy and safety with eculizumab (Soliris), and 25 years of leadership in complement biology,” Alexion’s executive vice president and head of research & development, John Orloff, MD, said in a recent statement.

A highly innovative, longer-acting anti-C5 antibody that inhibits terminal complement, ALXN1210, previously received Orphan Drug Designation on January 6, 2017 by the FDA and June 1, 2016, by the European Union (EU). Since the submission uses a rare disease priority review voucher, the BLA is designated for an expedited review of 8 months compared with the usual 12 months.

Alexion supports their submission with data yielded from 2 phase 3 clinical trials conducted in upwards of 440 patients—the largest population of PNH patients ever studied; these patients included those who never received a complement inhibitor and those who were stable on eculizumab and transferred over to ALXN1210.

Patients were administered ALXN1210 every 8 weeks and the weight-optimized treatment was found to be noninferior to treatment with eculizumab every 2 weeks on all primary endpoints as well as key secondary endpoints across both trials.

Furthermore, Alexion reports that the numeric results for all endpoints, including breakthrough hemolysis, “favored ALXN1210 in both studies” and the results proved consistent with the immediate and complete C5 inhibition noted by the end of the first administration of ALXN1210 and was sustained throughout the entire treatment period, which was 26 weeks.

The investigators did not report any significant differences in the safety profiles of ALXN1210 and eculizumab.

PNH affects 1 to 1.5 persons per million of the population and is most common among younger adults. The disease is characterized by the obliteration of red blood cells, blood clots, and damaged bone marrow function. The median survival time after a PNH diagnosis is about 10 years, according to Johns Hopkins Medicine, but some patients are able to survive for decades with minimal symptoms.

Alexion plans on submitting for the approval of ALXN1210 as a treatment for PNH patients in the EU as well by mid-year as well as in Japan in the second half of this year.