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Soliris(R) Reduced Measures of Thrombosis and Inflammation, and Decreased Indicators of Pulmonary Hypertension, in Studies of Patients with PNH

December 9, 2008

CHESHIRE, Conn., Dec. 9 /PRNewswire-FirstCall/ — Soliris(R) (eculizumab),
a terminal complement inhibitor developed by Alexion Pharmaceuticals, Inc.
(Nasdaq: ALXN), was observed by investigators to reduce blood measures
associated with undiagnosed blood clots and inflammation in patients with PNH.

A separate study found that Soliris was observed to reduce indicators of
pulmonary artery hypertension (PAH) in patients with paroxysmal nocturnal
hemoglobinuria (PNH), according to a new analysis of clinical trial data. Both
sets of data were presented in oral sessions yesterday at the 50th Annual
Meeting of the American Society of Hematology.

“The common, severe and progressive clinical consequences of PNH are
becoming more apparent as researchers gain more experience and basic knowledge
with regard to this disease,” said Leonard Bell, M.D., Chief Executive Officer
of Alexion.

Blood Markers of Thrombin Generation and Inflammation

Research titled “Eculizumab Therapy Results in Rapid and Sustained
Decreases in Markers of Thrombin Generation and Inflammation in Patients with
PNH” was presented yesterday in an oral session at the ASH annual meeting by
Ilene Ceil Weitz, M.D., Assistant Clinical Professor of Medicine, Jane Anne
Nohl Division of Hematology, Keck School of Medicine of the University of
Southern California
.

Recently published research showed that patients with PNH were observed to
have 92 percent fewer blood clots (thromboses) during treatment with Soliris
(1) compared to the period of time prior to Soliris treatment. To better
understand the mechanism for this observed reduction, researchers used highly
sensitive laboratory tests to track levels of blood markers in order to
determine the effect of Soliris on markers of thrombin generation and
inflammation among eight patients with PNH, only one of which had been
previously diagnosed with a blood clot.

Results showed that prior to treatment with Soliris, patients with PNH
exhibited a hypercoagulable state as indicated by elevated levels of key
inflammatory and pro-thrombotic measures. Soliris treatment was associated
with statistically significant decreases in key blood measures, including LDH
levels (p=0.0001), D-dimers (p=0.0057), thrombin-antithrombin complex or TAT
(0.01), interleukin 6 or Il-6 (p=0.04), and tissue factor microparticles or
TFMP (0.02) during the four-week induction phase of treatment. All decreases
in D-dimers, TAT, Il-6, TFMP, and LDH were sustained in the maintenance phase
of treatment.

The authors concluded that the study patients, most of whom did not have
clinical evidence of thrombosis and were also not previously transfused,
exhibited a hypercoagulable state. In these patients, Soliris treatment was
observed to result in a decrease in measures of thrombin generation and
inflammation. These changes appeared to be independent of the observed
reduction in hemolysis.

“This data deepens our understanding of the complex interactions in the
blood that result in dangerous inflammation and blood clots in patients with
PNH,” said Dr. Weitz. “It also suggests that many patients with PNH, even
without a clinical thrombosis, exhibit a high risk for blood clotting, and
provides hope for patients and physicians, since thrombosis is the leading
cause of premature death in PNH and the most feared complication of the
disease.”

Pulmonary Hypertension

Research titled “Eculizumab Reduces Pulmonary Hypertension through
Inhibition of Hemolysis-Associated Nitric Oxide Consumption in Patients with
Paroxysmal Nocturnal Hemoglobinuria” was presented in an oral session
yesterday at the ASH annual meeting by Anita Hill, M.D., of the Department of
Haematology, Bradford Royal Infirmary, Bradford, United Kingdom.

Using data from the Phase III TRIUMPH study of Soliris, Dr. Hill and her
colleagues evaluated the efficacy of Soliris in the regulation of cell-free
plasma hemoglobin levels, nitric oxide depletion and subsequent cardiovascular
morbidities in patients with PNH. This analysis found that 47 percent of
patients with PNH (34 of 73) suffered from pulmonary hypertension before
starting the trial. In this study, PAH was measured by an elevated blood level
of NT-proBNP, which has been shown to be highly predictive of PAH and an
independent predictor of mortality in other hemolytic diseases. (2) At the
start of the study, levels of hemolysis and nitric oxide consumption were
shown to be much greater in PNH (more than 6- and 10-fold, respectively) than
in patients with other hemolytic diseases.

Patients treated with Soliris experienced a 50 percent reduction in the
incidence of PAH over the course of the 26-week treatment period, from 52.5
percent to 26.3 percent, while PAH did not change with placebo (39.4% to
43.8%) (P<0.001). Additionally, Soliris-treated PNH patients experienced
significantly improved shortness of breath compared to placebo, as measured by
the EORTC QLQ-C30 quality of life survey (P<0.001).

“A careful analysis of blood levels in PNH patients shows that hemolysis,
the red blood cell destruction that defines the disease, consumes nitric oxide
in the blood which is likely to result in an increase in cardiovascular
complications as shown in other hemolytic diseases,” said Dr. Hill. “This
study confirms that PAH is common in hemolytic PNH patients and also suggests
that the anti-hemolytic effect of Soliris treatment significantly increases
nitric oxide and consequently reduces pulmonary hypertension in patients with
PNH.”

Pulmonary artery hypertension is a rare, progressive disorder
characterized by high blood pressure (hypertension) of the pulmonary arteries,
the blood vessels that carry blood from the heart to the lungs. Symptoms of
pulmonary hypertension can be severe and include shortness of breath
(dyspnea), chest pain, fatigue, and fainting episodes.

Additional Data

A poster titled “Modification of the Eculizumab Dose to Successfully
Manage Intravascular Breakthrough Hemolysis in Patients with Paroxysmal
Nocturnal Hemoglobinuria” was presented yesterday at the ASH annual meeting by

Richard Kelly, M.D., of St. James’s University Hospital, Leeds, United
Kingdom
. The authors concluded that two alternative-dosing regimens of Soliris
were well tolerated and could be employed in the small percentage of patients
with PNH in whom complement inhibition is not consistently maintained using
the standard dose. For details, visit:
http://ash.confex.com/ash/2008/webprogram/Paper8331.html.

A poster titled “Reducing Intravascular Hemolysis on Ferritin Homeostasis
in Eculizumab Treated Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients” was
presented yesterday at the ASH annual meeting by Alexander Roeth, M.D. of the
Department of Hematology, University Hospital Essen in Essen, Germany. The
authors concluded that eculizumab was safe and well tolerated in the study
patients, and that iron parameters in PNH patients treated with eculizumab
should be monitored to determine if iron supplementation should be altered or
iron depletion therapy should be considered. For details, visit:
http://ash.confex.com/ash/2008/webprogram/Paper11166.html.

About PNH

PNH is a rare blood disorder that affects an estimated 8,000 to 10,000
people in North America and Europe and, using similar prevalence estimates,
potentially 1,000 – 2,000 patients in Japan. (3) PNH strikes people of all
ages, with an average age of onset in the early 30s. (4) Approximately 10
percent of all patients first develop symptoms at 21 years of age or younger.
(5) PNH develops without warning and can occur in men and women of all races,
backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis
ranging from one to more than 10 years. (6) The estimated median survival for
PNH patients is between 10 and 15 years from the time of diagnosis. (4,6)

PNH has been identified more commonly among patients with disorders of the
bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes
(MDS). (7, 8, 9). In patients with thrombosis of unknown origin, PNH may be
an underlying cause. (5,10)

Prior to approval of Soliris, there were no therapies specifically
available for the treatment of PNH. PNH treatment was limited to symptom
management through periodic blood transfusions, non-specific immunosuppressive
therapy and, infrequently, bone marrow transplantations — a procedure that
carries considerable mortality risk. (5,10)

About Soliris

Soliris was approved in March 2007 by the U.S. Food and Drug
Administration (FDA) as the first treatment for PNH, a rare, debilitating and
life-threatening blood disorder defined by hemolysis, or the destruction of
red blood cells. In June 2007, the European Commission (EC) also approved the
use of Soliris for the treatment of patients with PNH. Soliris is the first
therapy approved in Europe for the treatment of PNH and was the first
medicinal product to receive EC approval under the EMEA Accelerated Assessment
Procedure.

Important Safety Information

Soliris is generally well tolerated. The most frequent adverse events
observed in clinical studies were headache, nasopharyngitis (a runny nose),
back pain and nausea. Treatment with Soliris should not alter anticoagulant
management because the effect of withdrawal of anticoagulant therapy during
Soliris treatment has not been established.

The U.S. product label for Soliris also includes a boxed warning: “Soliris
increases the risk of meningococcal infections. Vaccinate patients with a
meningococcal vaccine at least two weeks prior to receiving the first dose of
Soliris; revaccinate according to current medical guidelines for vaccine use.
Monitor patients for early signs of meningococcal infections, evaluate
immediately if infection is suspected, and treat with antibiotics if
necessary.” During clinical studies, two out of 196 vaccinated PNH patients
treated with Soliris experienced a serious meningococcal infection.

Prior to beginning Soliris therapy, all patients and their prescribing
physicians are enrolled in the Soliris Safety Registry which is part of a
special risk management program that involves initial and continuing education
and long-term monitoring for detection of new safety findings.

Please see full prescribing information at www.soliris.net.

About Alexion

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company working to
develop and deliver life-changing drug therapies for patients with serious and
life-threatening medical conditions. Alexion is engaged in the discovery,
development and commercialization of therapeutic products aimed at treating
patients with a wide array of severe disease states, including hematologic
diseases, cancer, and autoimmune disorders. In March 2007, the FDA granted
marketing approval for Alexion’s first product, Soliris, for all patients with
PNH, and Alexion began commercial sale of Soliris in the U.S. during April
2007
. In June 2007, the EC granted marketing approval for Soliris in the
European Union for all patients with PNH. Alexion is evaluating other
potential indications for Soliris as well as other formulations of eculizumab
for additional clinical indications, and is pursuing development of other
antibody product candidates in early stages of development. This press release

and further information about Alexion Pharmaceuticals, Inc. can be found at:
www.alexionpharm.com.


    [ALXN-G]

Safe Harbor Statement

This news release contains forward-looking statements, including
statements related to potential health and medical benefits from Soliris.
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 Soliris, delays in arranging satisfactory
manufacturing capability and establishing commercial infrastructure, delays in
developing or adverse changes in commercial relationships, the possibility
that results of clinical trials are not predictive of safety and efficacy
results of Soliris in broader patient populations, the possibility that
initial results of commercialization are not predictive of future rates of
adoption of Soliris, the risk that third parties won’t agree to license any
necessary intellectual property to Alexion on reasonable terms or at all, the
risk that third party payors will not reimburse for the use of Soliris at
acceptable rates or at all, the risk that estimates regarding the number of
PNH patients are inaccurate, the risk that pending litigation may be resolved
adversely, 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 September 30, 2008 and in Alexion’s other filings with
the Securities and Exchange Commission. 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) Hillmen P, Muus P et al. Effect of the complement inhibitor
eculizumab on thromboembolism in patients. Blood. 2007;110:4123-4128)

(2) Machado RF, Anthi A, Martin et al. N-Terminal Pro-Brain Natriuretic
Peptide Levels and Risk of Death in Sickle Cell Disease. JAMA.
2006;296(3):310.

(3) Hill A, Platts PJ, Smith A et al. The incidence and prevalence of
paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in
Yorkshire [abstract]. Blood. 2006;108(11):985.

(4) Socie G, Mary J Yves, de Gramont A, et al. Paroxysmal nocturnal
haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996:
348:573-577.

(5) Parker C, Omine M, Richards S, et al. Diagnosis and management of
paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-3709.

(6) Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history
of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995; 333:1253-1258.

(7) Wang H, Chuhjo T, Yasue S, Omine M, Naka S. Clinical significance of a
minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone
marrow failure syndrome. Blood. 2002;100 (12):3897-3902.

(8) 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.

(9) Maciejewski JP, Risitano AM, Sloand EM, 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.

(10) Hill A, Richards S, Hillmen P. Recent developments in the
understanding and management of paroxysmal nocturnal haemoglobinuria. Br J
Haematol. 2007;137 (3):181-192.

SOURCE Alexion Pharmaceuticals, Inc.


Source: newswire



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