-- Use of Priority Review Voucher Provides
Expedited Review of Eight Months --
-- Submission in the European Union on Track
for Mid-Year and in Japan for the Second Half of the Year --
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the
submission of a Biologics License Application (BLA) to the U.S.
Food and Drug Administration (FDA) for approval of ALXN1210, the
Company’s investigational long-acting C5 complement inhibitor, for
the treatment of patients with paroxysmal nocturnal hemoglobinuria
(PNH). The submission uses a rare disease priority review voucher,
which designates the BLA for an expedited eight-month review by the
FDA instead of the standard 12-month review.
“This first regulatory submission is an important step toward
our goal of establishing ALXN1210 as the new standard of care for
patients with PNH, building on 10 years of proven efficacy and
safety with Soliris®, and 25 years of leadership in complement
biology,” said John Orloff, M.D., Executive Vice President and Head
of Research & Development at Alexion. “We look forward to
working with the FDA to facilitate a rapid review.”
The application is supported by comprehensive data from two
rigorous Phase 3 clinical trials in the largest population of
patients with PNH ever studied: 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. Weight-optimized treatment with ALXN1210 every eight
weeks demonstrated non-inferiority to treatment every two weeks
with Soliris® on all primary endpoints and key secondary endpoints
in both studies. The numeric results for all these endpoints,
including breakthrough hemolysis (one of the key secondary
endpoints), favored ALXN1210 in both studies and are 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 the BLA in the U.S., Alexion is preparing
submissions for the approval of ALXN1210 as a treatment for
patients with PNH in the European Union (EU) by mid-year and 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.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. 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
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
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.
[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 submission of regulatory
applications for review and approval by authorities in the US,
Japan and the European Union for ALXN1210, the timing of
anticipated future submissions of regulatory applications for ALXN
1210 for review and approval by certain governmental authorities,
the anticipated timing and the speed of the review of regulatory
applications for ALXN 1210 by governmental authorities, making
ALXN1210 the new standard of care for patients with PNH and the
potential medical benefits of ALXN1210 for the treatment of PNH.
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 ALXN
1210 for review and approval by certain governmental authorities in
the timeframes expected due to delays or future product
information, 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, potential
declines in sovereign credit ratings or sovereign defaults in
countries where we sell our products, 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 March 31, 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. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20180619005531/en/
Alexion Pharmaceuticals, Inc.MediaArne Naeveke, PhD,
475-230-3774OrInvestorsSusan Altschuller, PhD, 475-230-3534
Alexion Pharmaceuticals (NASDAQ:ALXN)
Historical Stock Chart
From Apr 2024 to May 2024
Alexion Pharmaceuticals (NASDAQ:ALXN)
Historical Stock Chart
From May 2023 to May 2024