First and Only Complement-based Therapy Approved for an Ultra-rare Subset of gMG
"Patients with refractory gMG have exhausted multiple therapies and
continue to suffer from severe symptoms and complications that markedly
impact their daily lives," said
Chronic uncontrolled activation of the complement cascade, a part of the immune system, can play a major role in the debilitating symptoms and potentially life-threatening complications of refractory gMG.8-10 Soliris is a first-in-class complement inhibitor that specifically and effectively inhibits the terminal part of the complement cascade.
"Our deep understanding of complement-mediated diseases enabled us to
develop Soliris for the treatment of patients with refractory gMG," said
Alexion's supplemental Biologics License Application (sBLA) in the
About Refractory Generalized Myasthenia Gravis
Patients with refractory generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive represent an ultra-rare subset of MG patients1-4 who continue to suffer from severe disease symptoms and complications despite therapies currently used for MG.1-2,11
MG is a debilitating, chronic and progressive autoimmune neuromuscular disease that can occur at any age but most commonly begins for women before the age of 40 and men after the age of 60.5,6,12,13 It typically begins with weakness in the muscles that control the movements of the eyeballs and eyelids, and often progresses to the more severe and generalized form, known as gMG with weakness of the head, neck, trunk, limb and respiratory muscles.13
While most symptoms in patients with gMG are managed with therapies for MG, 10% to 15% of patients are considered refractory—meaning they do not respond to multiple therapies for MG and continue to suffer profound muscle weakness, and severe disease symptoms that limit function.1-2,11 Patients with refractory gMG can suffer from slurred speech; impaired swallowing; double or blurred vision; disabling fatigue; immobility requiring assistance; shortness of breath, and episodes of respiratory failure. Complications, exacerbations and myasthenic crises can require hospital and intensive care unit admissions with prolonged stays and can be life-threatening.5-7
In patients with anti-AChR antibody-positive MG, the body's own immune system turns on itself to produce antibodies against AChR, a receptor located on muscle cells in the neuromuscular junction (NMJ) and used by nerve cells to communicate with the muscles these nerves control.5,6 The binding of these antibodies to AChR activates the complement cascade, another part of the immune system, which leads to a localized destruction of the NMJ. As a result, the communication between nerve and muscle is impaired, which in turn leads to a loss of normal muscle function.8-10,14
About Soliris® (eculizumab)
Soliris® is a first-in-class complement inhibitor that works by inhibiting the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in serious ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and anti-acetylcholine receptor (AChR) antibody-positive refractory generalized myasthenia gravis (gMG).
Soliris is approved in the
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
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.
This news release contains forward-looking statements, including
statements related to the potential medical benefits of Soliris®
(eculizumab) for the treatment of generalized myasthenia gravis (gMG),
Silvestri N, Wolfe G. Treatment-refractory myasthenia gravis.
J. ClinNeuromuscul Dis. 2014;15(4):167-178.
Howard J. Targeting the Complement System in Refractory Myasthenia
Gravis. Supplement to Neurology Reviews.
- Suh J., Goldstein JM, Nowak RJ. Clinical Characteristics of Refractory Myasthenia Gravis Patients. Yale J Biol Med. 2013;86(2):255-260.
Regulation (EU) No 536/2014 of the
European Parliamentand of the Council of 16 April 2014on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141&qid=1421232987002&from=EN. Accessed on June 26, 2017.
- Howard JF, Barohn RJ, Cutter GR, et al. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013;48(1):76-84.
National Institute of Neurological Disorders and Stroke. Myasthenia Gravis Fact Sheet. Publication date May 2017. http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm.
Sathasivam S. Diagnosis and management of myasthenia gravis. Progress
in Neurology and Psychiatry. January/
- Tüzün E, Huda R, Christadoss P. Complement and cytokine based therapeutic strategies in myasthenia gravis. JAutoimmun. 2011;37(2):136-143.
Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis:
beyond diagnosis? Expert
Rev. Clin.Immunol. 2012;8(5), 427-428.
- Conti-Fine, et al. Myasthenia gravis: past, present, and future. J Clin Invest. 2006; 116:2843-2354.
- Sanders DB, Wolfe, GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2016 Jul 26;87(4):419-25.
- Huda R, Tüzün E, Christadoss P. Targeting complement system to treat myasthenia gravis. Rev. Neurosci. 2014; 25(4): 575-583.
- Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009-8(5): 475-490.
Buzzard, K. A.,
N. J. Meyer, T. A. Hardy, D. S. Riminton and S. W. Reddel. Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis. Muscle Nerve. 2015;52(2): 204-210.
Arne Naeveke, PhD, 475-230-3774
Vice President, Investor Relations
Director, Investor Relations
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