First and Only Approved Complement Inhibitor in Japan as a Treatment
for Patients with gMG, a Chronic and Debilitating Neuromuscular Disorder
NEW HAVEN, Conn.--(BUSINESS WIRE)--
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today that the
Ministry of Health, Labour and Welfare (MHLW) in Japan has approved
Soliris® (eculizumab) as a treatment for patients with generalized
myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR)
antibody-positive and whose symptoms are difficult to control with
high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis
(PLEX). Soliris is the first and only complement inhibitor approved in
Japan as a treatment for these patients. In the Phase 3 REGAIN study and
its ongoing open-label extension study, Soliris demonstrated treatment
benefits for patients with anti-AChR antibody-positive gMG who had
previously failed immunosuppressive treatment and continued to suffer
from significant unresolved disease symptoms, which can include
difficulties seeing, walking, talking, swallowing and breathing.1,2,3
These patients are at an increased risk of disease exacerbations and
crises that may require hospitalization and intensive care and may be
"Soliris represents an important treatment advance for patients in Japan
with anti-AChR antibody-positive gMG who continue to suffer from
significant unresolved disease symptoms despite existing treatment
options," said John Orloff, M.D., Executive Vice President and Head of
Research & Development at Alexion. "We are proud that these patients
will be able to benefit from our deep understanding of complement
biology, which allowed us to develop Soliris as treatment for this
debilitating neuromuscular disorder."
Chronic uncontrolled activation of the complement system, a part of the
immune system, plays a major role in the debilitating symptoms and
potentially life-threatening complications for patients with gMG who are
anti-AChR antibody-positive.6,7,8 By selectively and
effectively inhibiting the terminal complement cascade, Soliris targets
a critical underlying cause of the disease.
"It is exciting that patients with gMG in Japan whose symptoms are
difficult to control will now have a new treatment option," said
Professor and Chairman Hiroyuki Murai, M.D., Ph.D., Department of
Neurology at the International University of Health and Welfare, School
of Medicine, Tokyo, Japan and an investigator in the clinical
development of this new indication. "I am pleased that the Ministry
appreciated the ability of Soliris to improve patients' symptoms, their
ability to carry out activities of daily living and their quality of
"This approval is great news for patients with gMG in Japan who fail to
adequately respond to existing therapies and continue to face
significant disease symptoms," said Michiyo Sakurai, President of the
Japanese Myasthenia Gravis Association, Kyoto, Japan. "The inability to
carry out activities of daily living can be very debilitating and
frustrating for these patients and their families and friends. They
welcome this new therapy option and the hope that it provides to them."
Japan's MHLW based its approval of this new indication of Soliris on
comprehensive clinical data from the Phase 3, randomized, double-blind,
placebo-controlled, multicenter REGAIN study (ECU-MG-301).
Soliris is also approved in the EU for the treatment of refractory gMG
in adults who are anti-AChR antibody-positive, and in the U.S. for the
treatment of adult patients with gMG who are anti-AchR antibody-positive.
About Generalized Myasthenia Gravis
Myasthenia gravis (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
60.1,9,10,11 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.11
In patients with anti-acetylcholine receptor (AchR) antibody-positive
MG, the body's own immune system turns on itself to produce antibodies
against AchR, a receptor located on muscle cells at the neuromuscular
junction (NMJ) and used by nerve cells to communicate with the muscles
these nerves control.6,7,8 The binding of these antibodies to
AchR activates the complement cascade, another part of the immune
system, which leads to a localized inflammation and destruction of the
muscle membrane at the NMJ. As a result, the communication between nerve
and muscle is impaired, which in turn leads to a loss of normal muscle
A subset of patients with anti-AchR antibody-positive gMG fails to
respond adequately to or cannot tolerate multiple therapies for MG and
continue to suffer profound muscle weakness, and severe disease symptoms
that limit function.12,13,14 These patients can suffer from
slurred speech, choking, impaired swallowing, double or blurred vision,
disabling fatigue, immobility requiring assistance, shortness of breath
and episodes of respiratory failure.1,2,3 Complications,
exacerbations and myasthenic crises can require hospital and intensive
care unit admissions with prolonged stays and can be life-threatening.4,5
Patients with anti-AchR antibody-positive gMG who continue to
suffer from severe disease symptoms and complications despite current
therapies for MG represent approximately 5-10% of all patients with MG.12,15,16,17
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 anti-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
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 Centers for Disease
Control (CDC)'s Advisory Committee on Immunization Practices (ACIP)
recommendations for meningococcal vaccination in patients with
complement deficiencies. Immunize patients with meningococcal vaccines
at least two weeks prior to administering the first dose of Soliris,
unless the risks of delaying Soliris therapy outweigh the risk of
developing a meningococcal infection. Monitor patients for early signs
of meningococcal infections and evaluate immediately if infection is
suspected. Soliris is available only through a restricted program under
a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris
REMS, prescribers must enroll in the program. Enrollment in the Soliris
REMS program and additional information are available by telephone:
1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.
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. Administration of Soliris may result
in infusion reactions, including anaphylaxis or other hypersensitivity
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
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.
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),
and Alexion's future clinical, regulatory and commercial plans for
Soliris for the treatment of myasthenia gravis. Forward-looking
statements are subject to factors that may cause Alexion's results and
plans to differ from those expected, including for example, the risks
and uncertainties of drug development, decisions of regulatory
authorities regarding the adequacy of our research, marketing approval
or material limitations on the marketing of our products, delays,
interruptions or failures in the manufacture and supply of our products
and our product candidates, failure to satisfactorily address matters
raised by the FDA and other regulatory agencies, the possibility that
the current rates of adoption of Soliris in paroxysmal nocturnal
hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or
other diseases are not sustained, the possibility that results of
clinical trials are not predictive of safety and efficacy results of our
products in broader patient populations, the possibility that clinical
trials of our product candidates could be delayed, the adequacy of our
pharmacovigilance and drug safety reporting processes, the risk that
third party payers (including governmental agencies) will not reimburse
or continue to reimburse for the use of our products at acceptable rates
or at all, the outcome of challenges and opposition proceedings to our
intellectual property, assertion or potential assertion by third parties
that the manufacture, use or sale of our products infringes their
intellectual property, uncertainties surrounding legal proceedings,
company investigations and government investigations, including
investigations of Alexion by the U.S. Securities and Exchange Commission
(SEC) and U.S. Department of Justice (DOJ), the risk that anticipated
regulatory filings are delayed, the risk that estimates regarding the
number of patients with PNH, aHUS, gMG, hypophosphatasia (HPP) and
lysosomal acid lipase deficiency (LAL-D) are inaccurate, the risks of
changing foreign exchange rates, risks relating to the potential effects
of the Company's restructuring and relocation of its corporate
headquarters, and a variety of other risks set forth from time to time
in Alexion's filings with the SEC, including but not limited to the
risks discussed in Alexion's Quarterly Report on Form 10-Q for the
period ended September 30, 2017 and in our other filings with the U.S.
Securities and Exchange Commission. Alexion does not intend to update
any of these forward-looking statements to reflect events or
circumstances after the date hereof, except when a duty arises under law.
1 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.
2National 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.
Accessed October 12, 2017
3 Sathasivam S. Diagnosis and
management of myasthenia gravis. Progress in Neurology and Psychiatry.
4 Souayah N, Nasar A, Suri MF, et
al. Trends in Outcomes and Hospitalization Charges among Mechanically
Ventilated Patients with Myasthenia Gravis in the United States. Int
J Biomed Sci. 2009;5(3):209-214.
5Engel-Nitz N, et
al. Clinical Burden of Refractory Generalized Myasthenia Gravis in the
United States. Poster 146; ICNMD 2016.
6 Conti-Fine, et
al. Myasthenia gravis: past, present, and future. J Clin Invest.
7 Tüzün E, Huda R, Christadoss P.
Complement and cytokine based therapeutic strategies in myasthenia
gravis. J Autoimmun. 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.
Huda R, Tüzün E, Christadoss P. Targeting complement system to treat
myasthenia gravis. Rev. Neurosci. 2014; 25(4): 575-583.
10National 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.
Accessed October 12, 2017
11 Meriggioli MN, Sanders DB.
Autoimmune myasthenia gravis: emerging clinical and biological
heterogeneity. Lancet Neurol. 2009-8(5): 475-490.
Silvestri N, Wolfe G. Treatment-refractory myasthenia gravis. J. Clin
Neuromuscul Dis. 2014;15(4):167-178.
13 Howard J.
Targeting the Complement System in Refractory Myasthenia Gravis. Supplement
to Neurology Reviews. February 2016.
Sanders DB, Wolfe, GI, Benatar M, et al. International consensus
guidance for management of myasthenia gravis: Executive summary. Neurology.
15 Suh J., Goldstein JM, Nowak RJ.
Clinical Characteristics of Refractory Myasthenia Gravis Patients. Yale
J Biol Med. 2013;86(2):255-260.
16 Howard J.
Myasthenia Gravis - A summary. Myasthenia Gravis Foundation of America. http://www.myasthenia.org/HealthProfessionals/ClinicalOverviewofMG.aspx.
Accessed October 12, 2017
17 Grob D, Brunner N, Namba T,
Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171226005046/en/
Alexion Pharmaceuticals, Inc.
Arne Naeveke, PhD,
Executive Director, Product Communications
Ridloff, CFA, 475-230-3601
Vice President, Investor Relations
Director, Investor Relations
Source: Alexion Pharmaceuticals, Inc.
News Provided by Acquire Media