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Alexion Submits Application for Priority Review and Approval of ALXN1210 as a Treatment for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the U.S.

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

___________________________

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understanding and management of paroxysmal nocturnal haemoglobinuria. Br
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2 Hillmen P, Lewis SM, Bessler M, et al. Natural history of
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9 Wang H, Chuhjo T, Yasue S, et al. Clinical significance of
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10 Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal
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11 Maciejewski JP, Rivera C, Kook H, et al. Relationship
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