Alexion Submits Application for Approval of ALXN1210 as a Treatment for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the European Union (EU)

-- EU Filing Follows U.S. Filing in June 2018 --

-- Submission in Japan on Track for the Second Half of the Year --

NEW HAVEN, CT, USA I June 28, 2018 I Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the submission of a Marketing Authorization Application to the European Medicines Agency (EMA) for ALXN1210, the Company’s investigational long-acting C5 complement inhibitor, for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). The application is supported by comprehensive data from two rigorous Phase 3 clinical trials in the largest population of patients with PNH ever studied in Phase 3: 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.

“We are excited about this next important step toward our goal of establishing ALXN1210 as the new standard of care for patients with PNH, following our recent submission in the U.S.,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “Building on 10 years of proven efficacy and safety with Soliris®, and 25 years of leadership in complement biology, our Phase 3 studies enrolled a very broad patient population, representative of those with PNH in clinical practice, including patients with a history of aplastic anemia, ‘classic’ PNH, as well as transfused and non-transfused patients. We look forward to working with European regulators to facilitate a smooth review.”

In two rigorous and large Phase 3 clinical studies, treatment with weight-based dosing of ALXN1210 every eight weeks demonstrated non-inferior results to treatment every two weeks with Soliris® on all 11 primary and key secondary endpoints in both studies. All endpoints, including breakthrough hemolysis (one of the key secondary endpoints), had point estimates that favored ALXN1210, which was 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 this submission in the European Union (EU) and the submission in the U.S. on June 18, Alexion is preparing a submission for a New Drug Application for ALXN1210 as a treatment for patients with PNH 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. 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. 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.

About ALXN1210

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.

About Soliris® (eculizumab)

Soliris® is a first-in-class complement inhibitor that works by inhibiting the C5 protein in the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in severe rare and ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Soliris® is approved in the U.S., EU, Japan, and other countries as the first and only treatment for patients with PNH and aHUS, in the EU as the first and only treatment of refractory generalized MG (gMG) in adults who are anti-AchR antibody-positive, in the U.S. for the treatment of adult patients with gMG who are anti-AchR antibody-positive, and in Japan for the treatment of patients with gMG who are AChR antibody-positive and whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis (PLEX). Soliris® is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).

Soliris® has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, Japan, and many other countries, for the treatment of patients with aHUS in the U.S., EU, and many other countries, for the treatment of patients with MG in the U.S. and EU, and for the treatment of patients with refractory gMG in Japan. Alexion and Soliris® have received some of the pharmaceutical industry's highest honors for the medical innovation in complement inhibition: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

For more information on Soliris®, please see full prescribing information for Soliris®, including BOXED WARNING regarding risk of serious meningococcal infection, available at www.soliris.net

About Alexion

Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the innovation, development and commercialization of life-changing therapies. Alexion is the global leader in complement inhibition and has developed and commercializes the first and only approved complement inhibitor to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG). In addition, Alexion has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). As the leader in complement biology for over 20 years, Alexion focuses its research efforts on novel molecules and targets in the complement cascade, and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, and metabolic disorders. This press release and further information about Alexion can be found at: www.alexion.com.

References

1 Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007 May;137(3):181-92.

2 Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. NEngl J Med. 1995 Nov 9;333(19):1253-8.

3 Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996;348:573-577.

4 Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121:4985-4996.

5 Nishimura J, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore) 2004 May;83(3):193-207.

6 Weitz I, Meyers G, Lamy T, et al. Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria. Intern Med J. 2013;43:298-307.

7 Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1;106(12):3699-709.

8 Hillmen P, Muus P, Duhrsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8.

9 Wang H, Chuhjo T, Yasue S, et al. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100 (12):3897-3902.

10 Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-474.

11 Maciejewski JP, Rivera C, Kook H, et al. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015-1022.

SOURCE: Alexion Pharmaceuticals

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