-- EU Filing Accepted and Under Review --
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today that
the U.S. Food and Drug Administration (FDA) has accepted for review
the Company’s Biologics License Application (BLA) for approval of
ALXN1210, the Company’s investigational long-acting C5 complement
inhibitor, for the treatment of patients with paroxysmal nocturnal
hemoglobinuria (PNH). The FDA set a Prescription Drug User Fee Act
(PDUFA) date of February 18, 2019, as part of an expedited
eight-month review instead of the standard 12-month review
following Alexion’s use of a rare disease priority review voucher.
The application is supported by comprehensive data from two
rigorous Phase 3 clinical trials.
“We are working with the FDA to facilitate a smooth review,”
said John Orloff, M.D., Executive Vice President and Head of
Research & Development at Alexion. “Building on comprehensive
results from the largest-ever Phase 3 development program in PNH,
11 years of proven efficacy and safety with Soliris®, and 25 years
of leadership in complement biology, we are on track with our
efforts to establish ALXN1210 as the new standard of care for
patients with PNH.”
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 March 15, 2018 and April 26, 2018,
respectively.
In addition to the submission in the U.S. on June 18 and the
submission in the European Union (EU) on June 28, 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. The European Medicines Agency (EMA) has accepted and is
reviewing the submission for the EU. ALXN1210 has received Orphan
Drug Designation (ODD) in the U.S. and EU for the treatment of
patients with PNH.
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
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.
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.
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
reactions.
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.
About Alexion
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 Forbes list of the World's Most
Innovative Companies seven years in a row and is headquartered in
Boston, Massachusetts' Innovation District. The company also has
offices around the globe and serves patients in more than 50
countries. This press release and further information about Alexion
can be found at: www.alexion.com.
[ALXN-G]
Forward-Looking Statement
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 Japan) for
ALXN1210 for treatment of patients with PNH, the timing of
anticipated future submissions of regulatory applications for
ALXN1210 for review and approval by certain governmental
authorities, future plans to work with regulatory authorities to
facilitate a smooth review of the ALXN1210 marketing authorization
application, making ALXN1210 the new standard of care for patients
with PNH, plans for future clinical studies of ALXN1210 delivered
subcutaneously as a potential treatment for patients with PNH and
aHUS, and the potential medical benefits of ALXN1210 for the
treatment of PNH and other diseases. Forward-looking statements are
subject to factors that may cause Alexion's results and plans to
differ materially from those expected by these forward looking
statements, including for example: the inability to submit
regulatory applications for ALXN1210 for review and approval by
certain governmental authorities in the timeframes expected due to
delays or future product information (or other reasons), the
inability to timely provide (or provide at all) the product safety
and efficacy information required by regulatory authorities for
products for certain indications, our products not gaining
acceptance among patients (and providers or third party payers) for
certain indications (due to cost or otherwise), the inability to
develop future clinical study programs for certain product delivery
mechanisms (or the failure of those programs to meet safety and
efficacy goals), the inability to timely and cost-effectively
develop programs for existing products for new indications (or the
failure to obtain regulatory approval for use in such new
indications), decisions of regulatory authorities regarding the
adequacy of our research, marketing approval or material
limitations on the marketing of our products (or the indications of
such 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 results of clinical
trials are not predictive of safety and efficacy results of our
products in broader patient populations, the possibility that
current rates of adoption of our products are not sustained (or do
not meet expected future rates), 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 (or
proposed future products) at acceptable rates or at all, delay of
collection or reduction in reimbursement due to adverse economic
conditions or changes in government and private insurer regulations
and approaches to reimbursement, 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, the risk
that other anticipated regulatory filings are delayed, the risk
that estimates regarding the number of patients with the diseases
that our products treat are inaccurate, 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 June 30, 2018
and in Alexion's other filings with the SEC. Alexion disclaims any
obligation to update any of these forward-looking statements to
reflect events or circumstances after the date hereof, except when
a duty arises under law.
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. N Engl 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.
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Alexion Pharmaceuticals, Inc.MediaArne Naeveke, PhD,
857-338-8597orInvestorsSusan Altschuller, PhD, 857-338-8788
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