With Eculizumab Biosimilars Closing in, Alexion Granted Priority Review for ALXN1210

This week, Alexion Pharmaceuticals announced that the FDA has accepted for review a Biologics License Application for ALXN1210, a proposed long-acting C5 complement inhibitor, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Alexion says that it expects a regulatory decision on the product in February 2019.

PNH is an ultra-rare blood disorder that causes uncontrolled activation of the complement system and results in hemolysis—the destruction of red blood cells—which, in turn, can cause thrombosis, potentially leading to organ damage and early death.

Alexion’s existing C5 complement inhibitor, eculizumab (Soliris), is currently used to treat patients with PNH, but the biologic must be administered every 2 weeks (versus ALXN1210’s proposed 8-week intravenous dosing schedule, and a proposed once-weekly subcutaneous dosing option that will be the subject of an upcoming phase 3 study).

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Earlier this year, Alexion reported positive topline results from a phase 3 study that determined that patients receiving treatment with eculizumab can be safely and effectively switched to treatment with ALXN1210. In addition to demonstrating noninferiority to eculizumab in terms the primary endpoint—change in lactate dehydrogenase levels—the proposed drug was also noninferior to eculizumab in the proportion of patients with breakthrough hemolysis, change from baseline in quality of life as determined via the Functional Assessment of Chronic Illness Therapy Fatigue Scale, the proportion of patients avoiding transfusion, and the proportion of patients with stable hemoglobin levels.

Alexion’s executive vice president and head of research and development, John Orloff, MD, said in a statement that the company hopes to “establish ALXN1210 as the new standard of care for patients with PNH,” but it will remain to be seen whether payers will agree that a longer duration of action is worth a potentially higher cost; the brand-name Soliris already carries a list price of approximately $500,000 per patient per year, making the biologic one of the most expensive therapies in the world.

However, biosimilars for eculizumab may be on the horizon. The reference eculizumab, which is also approved to treat 2 other ultra-rare disorders, atypical hemolytic uremic syndrome and myasthenia gravis, is expected to lose patent protection in the United States and Europe within 3 years’ time.

The molecule is targeted by at least 1 biosimilar developer; Amgen is currently engaged in a phase 3 study in Spain that evaluates the efficacy and safety of its proposed biosimilar, ABP 959, versus the reference eculizumab in patients with PNH.