Alexion Pharmaceuticals has submitted a Biologics License Application (BLA) to the YOU.S. 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.The submission uses a rare disease priority review voucher, which designates the BLA for an expedited eight-month review by the FDA instead of the standard 12-month review.
“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 Soliris®, and 25 years of leadership in complement biology,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “We look forward to working with the FDA to facilitate a rapid review.”
The application is supported by comprehensive data from two rigorous Phase 3 clinical trials in the largest population of patients with PNH ever studied: more than 440 patients, which included patients who had never received a complement inhibitor, and patients who were stable on Soliris® (eculizumab) and switched to ALXN1210. Weight-optimized treatment with ALXN1210 every eight weeks demonstrated non-inferiority to treatment every two weeks with Soliris® on all primary endpoints and key secondary endpoints in both studies. The numeric results for all these endpoints, including breakthrough hemolysis (one of the key secondary endpoints), favored ALXN1210 in both studies and are consistent with the immediate and complete C5 inhibition observed by the end of the first infusion of ALXN1210 and sustained throughout the entire 26-week treatment period. There were no notable differences in the safety profiles for ALXN1210 and Soliris®. Topline data of these Phase 3 studies were disclosed in press releases on March 15, 2018 and April 26, 2018, respectively.
In addition to the BLA in the U.S., Alexion is preparing submissions for the approval of ALXN1210 as a treatment for patients with PNH in the European Union (EU) by mid-year and in Japan in the second half of the year. ALXN1210 has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S. and EU.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating, and potentially life-threatening ultra-rare blood disorder that can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,2,3 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.2 In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis (the destruction of red blood cells)4, which in turn can result in progressive anemia, fatigue, dark urine, and shortness of breath.5,6,7 The most devastating consequence of chronic hemolysis is thrombosis (the formation of blood clots), which can damage vital organs and cause premature death.8 Historically, it had been estimated that one in three patients with PNH did not survive more than five years from the time of diagnosis.2 PNH is more common among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).9,10,11 In certain patients with thrombosis of unknown origin, PNH may be an underlying cause.4
ALXN1210 is an innovative, long-acting C5 inhibitor discovered and developed by Alexion that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). In Phase 3 clinical studies in complement inhibitor-naïve patients with PNH, and patients with PNH who had been stable on Soliris®, intravenous treatment with ALXN1210 every eight weeks demonstrated non-inferiority to intravenous treatment with Soliris® every two weeks, with numeric results for all primary and key secondary endpoints favoring ALXN1210. ALXN1210 is also currently being evaluated in a Phase 3 clinical study in complement inhibitor-naïve patients with aHUS, administered intravenously every eight weeks. In addition, Alexion plans to initiate a Phase 3 clinical study of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS. Alexion also plans to initiate the development of ALXN1210 as a potential treatment for patients with generalized MG (gMG) and patients with immunoglobulin A nephropathy (IgAN).
ALXN1210 has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S. and EU, and for the subcutaneous treatment of patients with aHUS in the U.S.