FDA Accepts Priority Review of ALXN1210 as a Treatment for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the US
-- EU Filing Accepted and Under Review --
“We are working with the
If approved, ALXN1210 would be the first and only long-acting complement
inhibitor for patients with PNH, providing immediate and complete
inhibition of the C5 complement protein that is sustained over an
eight-week dosing interval. The Phase 3 clinical development program of
ALXN1210 is the largest-ever Phase 3 program in PNH. The studies
enrolled a very broad and diverse population of more than 440 patients,
which included patients who had never been treated with a complement
inhibitor and patients who were stable on Soliris® and
switched to ALXN1210. Topline data were disclosed in press releases on
In addition to the submission
in the U.S. on
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.
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,
Soliris® has received Orphan Drug Designation (ODD) for the
treatment of patients with PNH in the U.S., EU,
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.
Important Soliris® Safety Information
The U.S. prescribing information for Soliris® includes the
following warnings and precautions: Life-threatening and fatal
meningococcal infections have occurred in patients treated with Soliris®.
Meningococcal infection may become rapidly life-threatening or fatal if
not recognized and treated early. Comply with the most current
Patients may have increased susceptibility to infections, especially
with encapsulated bacteria. Aspergillus infections have occurred in
immunocompromised and neutropenic patients. Children treated with Soliris®
may be at increased risk of developing serious infections due to Streptococcus
pneumoniae and Haemophilus influenza type b (Hib). Soliris®
treatment of patients with PNH should not alter anticoagulant management
because the effect of withdrawal of anticoagulant therapy during Soliris®
treatment has not been established.
In patients with PNH, the most frequently reported adverse events observed with Soliris® treatment in clinical studies were headache, nasopharyngitis, back pain, and nausea. In patients with aHUS, the most frequently reported adverse events observed with Soliris® treatment in clinical studies were headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia. In patients with gMG who are anti-AchR antibody-positive, the most frequently reported adverse reaction observed with Soliris® treatment in the placebo-controlled clinical study (≥10%) was musculoskeletal pain.
Alexion is a global biopharmaceutical company focused on serving
patients and families affected by rare diseases through the discovery,
development, and commercialization of life-changing therapies. As the
global leader in complement biology and inhibition for more than 20
years, Alexion 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). Alexion also 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). In addition, the
company is developing two late-stage therapies, a second complement
inhibitor and a copper-binding agent for Wilson disease. 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. Alexion has
been named to the
This press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements related to: the future planned submission of
regulatory applications for review and approval by regulatory
authorities in certain countries (including
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. N Engl J Med. 1995
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
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
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
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.
Alexion Pharmaceuticals, Inc.
Arne Naeveke, PhD, 857-338-8597
Susan Altschuller, PhD, 857-338-8788