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FDA Accepts Priority Review of ALXN1210 as a Treatment for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the US

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-- 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

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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.
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4 Hill A, Kelly RJ, Hillmen P.
Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood.
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5 Nishimura J, Kanakura Y, Ware RE,
et al. Clinical course and flow cytometric analysis of paroxysmal
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6 Weitz I, Meyers G,
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Med J
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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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