FDA Grants Breakthrough Therapy Designation to Asfotase Alfa for Perinatal-, Infantile- and Juvenile-Onset Hypophosphatasia (HPP

  FDA Grants Breakthrough Therapy Designation to Asfotase Alfa for Perinatal-,
  Infantile- and Juvenile-Onset Hypophosphatasia (HPP)

Business Wire

LAUSANNE, Switzerland -- May 28, 2013

Alexion Pharma International Sàrl, a subsidiary of Alexion Pharmaceuticals,
Inc. (Nasdaq: ALXN), today announced that the U.S. Food and Drug
Administration (FDA) has granted Breakthrough Therapy designation to asfotase
alfa for the treatment of patients with hypophosphatasia (HPP) whose first
signs or symptoms occurred prior to 18 years of age, including perinatal-,
infantile-, and juvenile-onset forms of the disease. HPP is an inherited,
life-threatening, ultra-rare metabolic disorder that leads to progressive
damage to multiple vital organs, including destruction and deformity of bones.

The FDA also confirmed that adult-onset HPP is “a serious and life threatening
disease or condition” and that Breakthrough Therapy designation could be
obtained for this aspect of the disease with additional clinical information.

According to the FDA, a Breakthrough Therapy designation is designed to
expedite the development of a drug to treat a serious or life-threatening
disease when preliminary clinical evidence indicates that the drug may
demonstrate substantial improvement over existing therapies on one or more
clinically significant endpoints. The Breakthrough Therapy designation is part
of the FDA Safety and Innovation Act (FDASIA) of 2012.^1

“The FDA’s Breakthrough Therapy designation for perinatal-, infantile- and
juvenile-onset HPP recognizes the severe, debilitating and life-threatening
nature of the disease, the clear unmet medical need of patients, and the
clinical evidence collected to date on asfotase alfa,” said Martin Mackay,
Ph.D., Executive Vice President, Global Head of R&D at Alexion. “Asfotase alfa
is a highly innovative therapeutic candidate with the potential to transform
the lives of patients with HPP who currently have no treatment options and
often receive only palliative care for this life-threatening disease.”

Alexion looks forward to working closely with the FDA and obtaining FDA
guidance on the subsequent development of asfotase alfa for the treatment of
HPP, including obtaining advice on generating evidence needed to support
approval of the drug in an efficient manner. Clinical studies of asfotase alfa
are ongoing for patients with HPP whose first signs or symptoms occurred prior
to 18 years of age, including perinatal-, infantile- and juvenile-onset forms
of HPP.

About Hypophosphatasia (HPP)

HPP is a life-threatening, genetic, and ultra-rare metabolic disease
characterized by defective bone mineralization and impaired phosphate and
calcium regulation that can lead to progressive damage to multiple vital
organs including destruction and deformity of bones, profound muscle weakness,
seizures, impaired renal function, and respiratory failure.^2-5

HPP is caused by a genetic deficiency of an enzyme known as tissue
non-specific alkaline phosphatase (TNSALP), which causes life-long
abnormalities in metabolism of two minerals, calcium and phosphate, leading
directly to the debilitating morbidities and premature mortality of the

The genetic deficiency in HPP can affect people of all ages.^2 HPP is
traditionally classified by the age of the patient at the onset of the
disease. Patients with perinatal-onset HPP manifest their first signs of
disease in utero or at birth. This form of the disease is usually lethal and
often leads to death in-utero. Those patients who survive birth often have
severely compromised respiratory function. ^ 6

Patients with infantile-onset HPP develop their first signs or symptoms of HPP
before 6 months of age. Individuals with this form of disease develop skeletal
abnormalities and may present with failure to thrive and respiratory failure
within the first 6 months of post-natal life. The prognosis of these patients
is very poor with mortality estimated at 50%.^2

Patients with juvenile-onset HPP exhibit their first signs or symptoms of HPP
after 6 months of age and before 18 years of age.Individuals with this form
of the disease are at risk for respiratory complications, painful fractures
and can have delayed acquisition of age-appropriate motor skills due to
hypo-mineralization and muscle weakness leading to need for walking
assistance; some may never walk.^2

About Asfotase Alfa

Asfotase alfa is an investigational, highly innovative, first-in-class
targeted enzyme replacement therapy. Asfotase alfa is designed to address the
underlying cause of HPP by normalizing the genetically defective metabolic
process, and preventing or reversing the severe and life-threatening
complications of life-long dysregulated mineral metabolism.

About Alexion

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on
serving patients with severe and ultra-rare disorders through the innovation,
development and commercialization of life-transforming therapeutic products.
Alexion is the global leader in complement inhibition, and has developed and
markets Soliris^® (eculizumab) as a treatment for patients with paroxysmal
nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS),
two debilitating, ultra-rare and life-threatening disorders caused by chronic
uncontrolled complement activation. Soliris is currently approved in more than
35 countries for the treatment of PNH, and in the United States and the
European Union for the treatment of aHUS. Alexion is evaluating other
potential indications for Soliris and is developing four other highly
innovative biotechnology product candidates, including asfotase alfa. This
press release and further information about Alexion Pharmaceuticals, Inc. can
be found at: www.alexionpharma.com.


Safe Harbor Statement

This news release contains forward-looking statements, including statements
related to potential medical benefits of asfotase alfa for hypophosphatasia
(HPP). Forward-looking statements are subject to factors that may cause
Alexion's results and plans to differ from those expected, including, for
example, decisions of regulatory authorities regarding marketing approval or
material limitations on the marketing of asfotase alfa for HPP, delays in
arranging satisfactory manufacturing capabilities and establishing commercial
infrastructure for asfotase alfa for HPP, the possibility that results of
clinical trials are not predictive of safety and efficacy results of asfotase
alfa in broader or different patient populations, the risk that third party
payors (including governmental agencies) will not reimburse for the use of
asfotase alfa (if approved) at acceptable rates or at all, the risk that
estimates regarding the number of patients with asfotase alfa and observations
regarding the natural history of patients with asfotase alfa are inaccurate,
and a variety of other risks set forth from time to time in Alexion's filings
with the Securities and Exchange Commission, including but not limited to the
risks discussed in Alexion's Quarterly Report on Form 10-Q for the period
ended March 31, 2013. 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.  Public Law 112-144. U.S. Government Printing Office, July 9, 2012.
     Whyte MP. Hypophosphatasia. In: Glorieux FH, Jueppner H, Pettifor J, eds.
2.   Pediatric bone: biology and diseases. 3rd ed. San Diego, CA: Academic
     Press, 2012: 771-94.
3.   Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with
     Hypophosphatasia. Arch Dis Child. 1990; 65(1):130-1.
     Whyte MP. Hypophosphatasia: nature's window on alkaline phosphatase
4.   function in humans. In: Principles of Bone Biology, 3rd Ed. Part II,
     Chapter 73: Molecular Mechanisms of Metabolic Bone Disease, Academic
     Press, 2008: 1573-98.
5.   Silver MM, Vilos GA, Milne KJ. Pulmonary hypoplasia in neonatal
     hypophosphatasia. Pediatr Pathol. 1998; 8:483-93.
     Whyte MP. Hypophosphatasia and the extracellular metabolism of inorganic
6.   pyrophosphate: Clinical and laboratory aspects. Crit Rev Clin Lab Sci.
     1991; 23:175-195.


Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Exec. Director, Corporate Communications
Rx Communications
Rhonda Chiger, 917-322-2569
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