Soliris® Reduced Hemolysis, Decreased Transfusion Requirements and Improved Fatigue in Patients with PNH and Bone Marrow Insufficiency Disorders
Adding Soliris to Immunosuppressive Therapy Provided Clinical Benefit
to Patients with Concomitant PNH and Aplastic Anemia in Study Presented
at ASH Annual Meeting Abstract 3012, Poster Board II-988
CHESHIRE, Conn., Dec 06, 2009 (BUSINESS WIRE) -- Soliris(R)
(eculizumab), a first-in-class terminal complement inhibitor
developed by Alexion
Pharmaceuticals, Inc. (Nasdaq: ALXN), reduced hemolysis (destruction
of red blood cells) and transfusion requirements, and improved measures
of fatigue, when added to ongoing immunosuppressive therapy (IST) in
patients with both paroxysmal
nocturnal hemoglobinuria (PNH) and bone marrow insufficiency (BMI),
including aplastic anemia (AA).
The data were presented today at the 51st
Annual Meeting of the American Society of Hematology in New Orleans
in a poster session titled, "Effects
of Eculizumab Therapy in Patients with Paroxysmal Nocturnal
Hemoglobinuria (PNH) Receiving Concurrent Immunosuppressive Therapy for
Bone Marrow Insufficiency."
In the study, patients with concomitant BMI and PNH treated with IST,
prior to addition of Soliris, continued to suffer increased hemolysis
and fatigue, contributing to PNH-related morbidities. In addition, the
study showed that patients with BMI and PNH, in which Soliris treatment
was added to ongoing immunosuppressive therapy, experienced a
substantial reduction in hemolysis and fatigue, and subsequent
morbidities.
"PNH and bone marrow insufficiency diseases like aplastic anemia have
distinctive disease morbidities and mortality and require specific
treatments," said Hubert Schrezenmeier, M.D., lead author of the study
and Professor of Medicine at the Institute of Transfusion Medicine at
the University of Ulm in Germany. "This clinical analysis showed
patients already receiving immunosuppressive therapy can be safely
treated with eculizumab and experience the expected sharp reduction in
hemolysis, the underlying cause of PNH-related morbidities."
"In many patients with PNH, physicians must also manage aplastic anemia
or other bone marrow insufficiencies," said Stephen Squinto, Ph.D.,
Executive Vice President and Head of Research and Development at
Alexion. "The results presented today demonstrate the need to identify
and treat each of these conditions effectively and at the same time in
order to provide patients with optimal care."
Soliris is the first therapy approved for the treatment of patients with
PNH, a rare, debilitating and life-threatening blood disorder, to reduce
hemolysis. In patients with PNH, hemolysis can cause thromboses, kidney
disease, liver dysfunction, disabling fatigue, impaired quality of life,
recurrent pain, shortness of breath, pulmonary hypertension,
intermittent episodes of dark-colored urine (hemoglobinuria), and anemia.
Clinical Data
Researchers conducted a post-hoc analysis of data in the Soliris PNH
controlled clinical trials database to evaluate the safety and efficacy
of Soliris in a population of patients receiving concomitant IST. The
database included a total of 195 patients, of which 17 were receiving
IST.
Patients were subdivided into two treatment groups - those patients who
commenced Soliris treatment during ongoing IST and patients who
commenced IST during ongoing Soliris treatment. The clinical endpoints
measured included lactase dehydrogenase (LDH) level as a measurement of
hemolysis, number of transfusions, hemoglobin (Hgb) level, and
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
Score. Patients were followed and results were reported for months prior
to and during Soliris treatment.
Twelve patients (11 with AA; 1 pancytopenic) were treated with the
immunosuppressive treatment cyclosporine A (CSA) from 9.8 months to 13
years before Soliris treatment. Despite treatment with CSA and prior to
introduction of Soliris, patients in this group continued to experience
PNH related morbidities as measured by increased hemolysis (measured by
LDH; mean 1,368 U/L), severe fatigue (mean FACIT-Fatigue Score of 26.9)
and substantial transfusion requirements (mean 17 U/year per patient) at
3 months prior to Soliris.
Commencement of Soliris treatment in patients also treated with ongoing
IST was associated with a significant reduction in hemolysis (from a
mean LDH of 1,368 U/L at 3 months prior to Soliris treatment to LDH of
389 U/L at 3 months following initiation of Soliris treatment and
maintained at 379 U/L for at least 1 year following initiation of
Soliris treatment; p=0.002 at 3 and 12 months respectively). The
reduction in hemolysis associated with Soliris treatment also reduced
transfusion requirements (from a mean of 17 transfusion units/year at 12
months prior to Soliris treatment to a mean of 6 transfusion units/year
at 12 months following initiation of eculizumab treatment; p=0.02) and
maintained hemoglobin levels (mean of 9.2 Hgb g/dL at 12 months prior to
Soliris treatment to 9.1 Hgb g/dL at 12 months following initiation of
Soliris treatment). Soliris treatment also significantly improved
fatigue scores (from a mean FACIT-Fatigue Score of 26.8 at 12 months
prior to Soliris treatment to a mean FACIT-Fatigue Score of 36.3
following initiation of Soliris treatment; p=0.02) despite the
stabilization of hemoglobin and reduction in transfusions. The overall
and infection-related adverse event rates and serious adverse event
rates were similar to the overall clinical trial population and did not
increase over time.
About PNH
PNH is an ultra-rare blood disorder that strikes people of all ages,
with an average age of onset in the early 30s. (1) Patients with PNH
suffer from hemolysis (red blood cell destruction) which leads to
thromboses (blood clots), disabling fatigue, anemia, impaired quality of
life, pulmonary hypertension, shortness of breath, recurrent pain,
kidney disease and intermittent episodes of dark-colored urine
(hemoglobinuria). (2,3) Approximately 10 percent of all patients first
develop symptoms at 21 years of age or younger. (2) 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. (4) It is estimated that approximately
one-third of patients with PNH do not survive more than five years from
the time of diagnosis. (4) PNH has been identified more commonly among
patients with disorders of the bone marrow, including aplastic anemia
(AA) and myelodysplastic syndromes (MDS). (5,6,7) In patients with
thrombosis of unknown origin, PNH may be an underlying cause. (1) More
information on PNH is available at www.pnhsource.com.
About Soliris
Soliris has been approved by the U.S. Food and Drug Administration
(March 2007), the European Commission (June 2007), Health Canada
(January 2009) and Australia's Therapeutic Goods Administration
(February 2009) as the first treatment for all patients with PNH, an
ultra-rare, debilitating and life-threatening blood disorder defined by
chronic hemolysis, or the destruction of red blood cells. Prior to these
approvals, there were no therapies specifically available for the
treatment of PNH. Soliris is not expected to affect the aplastic
component of anemia in patients with PNH.
More information on Soliris is available at www.soliris.net.
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. Meningococcal
infection may become rapidly life-threatening or fatal if not recognized
and treated early. 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 encouraged to enroll in the PNH 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.
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 and kidney diseases, transplant, cancer, and
autoimmune disorders. Soliris is Alexion's first marketed product.
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.alexionpharma.com.
[ALXN-G]
Safe Harbor
This news release contains forward-looking statements, including
statements related to potential health and medical benefits from Soliris
(eculizumab). 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
published reports or clinical trials are not predictive of safety and
efficacy results of Soliris in broader patient populations, the risk
that clinical trials may not be completed successfully, 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, 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, 2009, 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.
References
1. Socié G, Mary J Yves, de Gramont A, et al. Paroxysmal nocturnal
haemoglobinuria: long-term follow-up and prognostic factors. Lancet.
1996: 348:573-577.
2. Parker C, Omine M, Richards S, et al. Diagnosis and management of
paroxysmal nocturnal hemoglobinuria. Blood. 2005;106
(12):3699-3709.
3. Hill A, Richards S, Hillmen P. Recent developments in the
understanding and management of paroxysmal nocturnal haemoglobinuria. Br
J Haematol. 2007;137:181-92.
4. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history
of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;
333:1253-1258.
5. 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.
6. 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.
7. 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.
SOURCE: Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
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