Soliris® Reduced Hemolysis, Lowered Thrombosis Rate and Improved Quality of Life in Patients with PNH Who Had Previously Never Been Transfused
Data Presented at ASH Annual Meeting Indicate that Transfusion
Requirements and Hemoglobin Levels May Not Adequately Reflect
Morbidities of PNHAbstract 4029, Poster Board III-965
CHESHIRE, Conn., Dec 07, 2009 (BUSINESS WIRE) -- New data presented today demonstrate the severe clinical burden of paroxysmal
nocturnal hemoglobinuria (PNH) and the clinical benefits of Soliris(R)
(eculizumab) in 44 patients with no history of prior blood
transfusions. Prior to Soliris treatment, these never-transfused
patients with PNH demonstrated increased intravascular hemolysis (red
blood cell destruction), 87% reported impaired quality of life, and 28%
had a history of clinically evident thrombosis (blood clots).
Soliris, a first-in-class terminal complement inhibitor developed by Alexion
Pharmaceuticals, Inc. (Nasdaq: ALXN), significantly reduced
hemolysis in all patients assessed in this retrospective study. 91% of
patients with quality of life assessments both before and during Soliris
treatment showed improvement in their quality of life during Soliris
treatment. Researchers also observed a significant reduction in
clinically evident thrombosis, from 7.85 events per 100 patient years to
zero events (p<0.001) following Soliris treatment.
The data were presented today at the 51st
Annual Meeting of the American Society of Hematology (ASH) in a
poster titled, "Clinical
Impact of Unregulated Terminal Complement Activity in Never-Transfused
Patients with Paroxysmal Nocturnal Hemoglobinuria."
"These data show that patients with PNH may have significant clinical
consequences from their disease, even if they did not have transfusion
requirements and even if hemoglobin levels were not significantly
decreased. In this study, nearly all patients with PNH and no prior
history of transfusions experienced intravascular hemolysis, which can
result in debilitating fatigue and impaired quality of life and serious
and life-threatening complications such as thrombosis, kidney damage,
and pulmonary hypertension," said Petra Muus, M.D., Ph.D. of Radboud
University, Nijmegen, Netherlands. "Soliris therapy inhibited hemolysis
in these patients, leading to immediate clinical benefit and potentially
reducing the long-term morbidity and mortality associated with this
ultra-rare disease."
"This study shows both the central role of unregulated complement
activity and chronic hemolysis in PNH, and the significant clinical
benefits of Soliris in all patients with PNH, regardless of
pre-treatment transfusion status or hemoglobin levels," said Leonard
Bell, M.D., Ph.D. Chief Executive Officer of Alexion.
Clinical Data
In this retrospective study, researchers identified and evaluated 44
patients with PNH who had not received prior red blood cell transfusions
and were considered candidates for Soliris therapy based on the
physician's clinical assessment. This group of patients from France,
Italy, the Netherlands, Australia and the United States ranged in age
from 16 to 84 years (median 41 years) and in duration of diagnosis from
1 month to 30 years (average 3.8 years). (1)
Prior to Soliris therapy, these never-transfused patients (n=44) overall
demonstrated increased intravascular hemolysis, as measured by elevated
LDH (median 1,360 U/L). Quality of life was assessed by a healthcare
provider and assessments included good (no impairment), or impairment
which was further characterized with any of the following terms: mild
impairment, disabling or moderate fatigue, disabling abdominal pain,
shortness of breath with exertion, or poor quality of life. In this
analysis, 87% of patients never transfused (34/39) had impaired quality
of life at baseline. Baseline levels of LDH (median 1,360 U/L),
hemoglobin (median 9.9 g/dL) and Type 3 white blood cell clone size
(median 70%) were not predictive of an association with impaired quality
of life, nor of history of thrombosis. In the study 52% of patients with
PNH and impaired quality of life had mild anemia (hemoglobin levels
greater-than or equal to 10.0g/dL) and 25% had a white blood cell clone size <50%. Clinically
evident thrombosis was relatively common, present in 28% of patients
overall. Baseline hemoglobin and clone size did not predict risk of TE.
The median hemoglobin level in those never transfused patients with a
history of thrombosis was 10.7 g/dL, with levels ranging from severe
anemia (8.0 g/dL) to normal levels (14.9 g/dL). Thrombosis was observed
in 33% of patients with PNH white blood cell clone size <50% (n=8) and
in 30% of patients with PNH white blood cell clone size >50% (n=24).
Patients received 600 mg of Soliris every 7 days (+/- 2 days) for 4
doses; followed by 900 mg one week later; then 900 mg every 14 days (+/-
2 days) for a median duration of 1.2 years. All patients who received
Soliris (n=27) experienced a reduction in hemolysis following treatment,
as measured by a median reduction in LDH from 1,603 U/L before treatment
to 380 U/L after treatment (p<0.0001). Among 11 patients who received a
quality of life assessment both before and after treatment, 91% reported
an impaired quality of prior to treatment, compared with none following
Soliris therapy. Further, there was no reported thrombosis during
treatment with eculizumab (11 patients with history of thrombosis) and
the thrombosis event rate was significantly reduced from 7.85 to 0
(events/100-patient years; p<0.001).
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. (2) 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). (3,4) Approximately 10 percent of all patients first
develop symptoms at 21 years of age or younger. (3) 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. (5) It is estimated that approximately
one-third of patients with PNH do not survive more than five years from
the time of diagnosis. (5) Studies have shown that kidney disease
accounts for 18 percent of deaths among Japanese patients with PNH. (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. (3) 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. 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 Statement
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.
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1. Muus P, et al. Clinical Impact of Unregulated Terminal Complement
Activity in Never-Transfused Patients with Paroxysmal Nocturnal
Hemoglobinuria. Presented at the 51st Annual Meeting of the American
Society of Hematology, New Orleans, LA December 7, 2009; Poster
Board # III-965 [Blood 2009; 114:4029]
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2. 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.
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3. Parker C, Omine M, Richards S, et al. Diagnosis and management of
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4. Hill A, Richards S, Hillmen P. Recent developments in the
understanding and management of paroxysmal nocturnal
haemoglobinuria. Br J Haematol. 2007;137:181-92.
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5. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural
history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;
333:1253-1258.
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6. Nishimura J, et al. Clinical course and flow cytometric analysis
of paroxysmal nocturnal hemoglobinuria in the United States and
Japan. Medicine 2004; 83 (3): 193-207.
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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.
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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.
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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.
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SOURCE: Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Sr. Director Corporate Communications
or
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