New Data Evaluating Asfotase Alfa in Infants and Young Children with Hypophosphatasia (HPP) Presented at Paediatric

  New Data Evaluating Asfotase Alfa in Infants and Young Children with
  Hypophosphatasia (HPP) Presented at Paediatric Endocrinology Meeting

- Early and Continued Improvement in Skeletal Mineralization Observed with 93%
Survival in Studied Patients -

- Patients Also Improved or Preserved Respiratory Function -

Business Wire

CHESHIRE, Conn. -- September 22, 2013

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that researchers
have presented data from an ongoing multinational Phase 2 study of asfotase
alfa in infants and young children with hypophosphatasia (HPP), an inherited,
ultra-rare metabolic disorder that in this patient population leads to
progressive damage to multiple vital organs, destruction and deformity of
bones, and death. ^ The study met its primary endpoint: infants and young
children with HPP treated with asfotase alfa had significant improvement in
skeletal mineralization from baseline as assessed radiographically after 24
weeks of treatment (p=0.001). This response was observed as early as 12 weeks
and improvement continued at 48 weeks. Ninety three percent of the patients
survived the first 48 weeks of treatment with 80% of patients having improved
respiratory status or requiring no respiratory support at the final analysis.
The data were presented in a late-breaking presentation at the 9^th Joint
Meeting of Paediatric Endocrinology in Milan, Italy.^1

“Hypophosphatasia is a genetic, very rare metabolic disease that can have
devastating and life-threatening consequences. HPP is characterized by
profound hypomineralization and a number of systemic effects, including
respiratory, neurologic and renal complications. Infants who develop their
first symptoms of HPP before 6 months of age have a very poor prognosis with
an estimated 50% mortality rate,” said lead investigator Dr. Cheryl R.
Greenberg, of the University of Manitoba in Winnipeg, Canada. “This study
showed that treatment with asfotase alfa improved bone mineralization in
infants and young children with HPP, and improved or preserved respiratory
function, which is often a cause of death in these patients.”

“We are excited about these results as they are consistent with previously
reported positive data now in a broader patient population of infants and
children,” said Martin Mackay, Ph.D. Executive Vice President, Global Head of
R&D at Alexion. “This further supports the potential of asfotase alfa as the
first treatment for HPP, and we look forward to completing our registration
program so that we may begin serving patients with this severe and often
life-threatening disease.”

Alexion is developing asfotase alfa as a potential treatment for HPP. Asfotase
alfa was used on an investigational basis in the reported study. The U.S. Food
and Drug Administration (FDA) recently designated asfotase alfa a Breakthrough
Therapy for the treatment of patients with HPP whose first signs or symptoms
occurred prior to 18 years of age, including perinatal-, infantile-, and
juvenile-onset forms of the disease.

About the Phase 2 Trial of Asfotase Alfa in HPP

Results were presented from an ongoing multinational, Phase 2, open-label
study that enrolled 15 infants and children with HPP (age 5 years or younger)
representing a range of HPP characteristics; of this number, 13 patients were
included in the Week 24 primary analysis. The median patient age at baseline
was 21.14 weeks (range: 0.1-304.0 weeks), and all patients had experienced
symptoms of HPP prior to 6 months old.^1

The primary efficacy endpoint of the study was change in skeletal
manifestations of HPP over time. The analysis presented today measured this
endpoint as changes in the severity of rickets (softening and weakening of
bones, which is unrelated to nutrition in patients with HPP) from baseline to
Week 24, as assessed by the Radiographic Global Impression of Change (RGI-C)
scale, a 7-point scale in which a rating of -3 represents severe worsening and
a rating of +3 indicates near or complete healing. Response to treatment was
defined as change from baseline in RGI-C of two or more points. Secondary
endpoints included changes in respiratory support status, overall survival,
and safety and tolerability.

Interim results presented today showed that the 13 evaluable patients treated
with asfotase alfa had a significant improvement from baseline to Week 24 in
skeletal mineralization, with a mean (standard deviation) increase in RGI-C
score of 1.74 (1.107) and a median increase of 2.00 (p=0.001). Response to
asfotase alfa therapy was evident as early as 12 weeks, with improvement
continuing to Week 48. Eight of 12 evaluable patients were characterized as
responders (defined as an RGI-C score of +2 [substantial healing] or greater)
at Week 24, and all 10 of the evaluable patients at Week 48 were responders.
Three patients had RGI-C scores of +3, which indicate near complete healing,
at both Weeks 24 and 48.^1

Additionally, the majority of patients (12/15) treated with asfotase alfa
improved or preserved respiratory function. Among the eight patients who
required respiratory support during the trial, five had improved by their last
assessment, and four patients no longer required any support. The overall
survival rate, another secondary endpoint, at 48 weeks was 93%. One patient in
the study withdrew consent after receiving two doses of asfotase alfa; this
patient later died from disease-related complications; the patient’s death was
deemed unrelated to the study drug.^1

Asfotase alfa was well-tolerated in the study with no deaths, serious adverse
events or discontinuations of therapy deemed related to treatment. The most
common adverse events were mild to moderate injection site reactions, reported
in 10 of the 15 patients (66.7%). These reactions included redness, (46.7%),
discoloration, (26.7%), and hardening of the skin (13.3%). The trial continues
to enroll patients and patients continue on treatment.^1

About Hypophosphatasia (HPP)

HPP is a chronic, 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.^3-6

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.^3 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.^7

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%.^3

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 profound muscle weakness 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.^3

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 potentially
life-threatening complications of life-long dysregulated mineral metabolism.

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.^8

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 PNH and aHUS,
two debilitating, ultra-rare and life-threatening disorders caused by chronic
uncontrolled complement activation. Soliris is currently approved in more than
40 countries for the treatment of PNH, and in the United States, Europe, Japan
and other territories for the treatment of aHUS. Alexion is evaluating other
potential indications for Soliris and is pursuing development of four other
innovative biotechnology product candidates which are being investigated
across additional severe and ultra-rare disorders beyond PNH and aHUS. This
press release and further information about Alexion Pharmaceuticals, Inc. can
be found at


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 June 30, 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.Greenberg CR, Vockley J, Harmatz P, Vallée M, Bedrosian CL, Liese JG.
    Asfotase alfa improves skeletal mineralization and respiratory function in
    infants and young children with hypophosphatasia: results from up to 12
    months’ treatment. Presented at the 9^th Joint Meeting of Paediatric
    Endocrinology, Milan, Italy, Sept. 22, 2013. Abstr. FC20-1488.
2.Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in
    life-threatening hypophosphatasia. N Engl J Med. 2012;366:904-13.
3.Whyte MP. Hypophosphatasia. In: Glorieux FH, Jueppner H, Pettifor J, eds.
    Pediatric bone: biology and diseases. 3rd ed. San Diego, CA: Academic
    Press, 2012: 771-94.
4.Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with
    Hypophosphatasia. Arch Dis Child. 1990; 65(1):130-1.
5.Whyte MP. Hypophosphatasia: nature's window on alkaline phosphatase
    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.
6.Silver MM, Vilos GA, Milne KJ. Pulmonary hypoplasia in neonatal
    hypophosphatasia. Pediatr Pathol. 1998; 8:483-93.
7.Whyte MP. Hypophosphatasia and the extracellular metabolism of inorganic
    pyrophosphate: Clinical and laboratory aspects. Crit Rev Clin Lab Sci.
    1991; 23:175-195.
8.Public Law 112-144. U.S. Government Printing Office, July 9, 2012.


Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Exec. Director, Corporate Communications
Alexion Pharmaceuticals, Inc.
Kim Diamond, 203-439-9600
Senior Director, Corporate Communications
Rx Communications
Rhonda Chiger, 917-322-2569
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