New Study Results Verify That PNH Cells Are Found in Majority of Patients with Bone Marrow Failure Syndromes
- Interim Results from EXPLORE Trial to be Presented at ASCO Annual
Meeting -
CHESHIRE, Conn., May 29, 2009 (BUSINESS WIRE) -- Paroxysmal nocturnal hemoglobinuria (PNH) cells are present in the
majority of patients with myelodysplastic syndromes (MDS), aplastic
anemia (AA), and other bone marrow failure syndromes (BMF), according to
interim results from 5,285 patients enrolled in the EXPLORE trial.
EXPLORE (EXamination of PNH, by Level Of
CD59 on REd and white blood cells) is the first large multicenter
study to determine the frequency of PNH cells in these patient
populations using a central laboratory conducting a high sensitivity
test for PNH cells. The findings from EXPLORE will be presented tomorrow
at the 45th Annual Meeting of the American Society of
Clinical Oncology (ASCO). The EXPLORE trial was sponsored by Alexion
Pharmaceuticals, Inc. (Nasdaq:ALXN).
PNH cells are defined as blood stem cells lacking certain proteins,
known as GPI-anchored proteins, which include proteins that ordinarily
protect blood cells from destruction by complement, a component of the
normal immune system. The lack of these complement inhibitors results in
the hemolysis (red blood cell destruction) that characterizes PNH, an
ultra-rare, debilitating and life-threatening disease.
"The true prevalence of PNH cells in patients with a number of bone
marrow failure syndromes has been unclear due to variability in PNH
testing. Interim results from the EXPLORE trial show that PNH cells are
common in these patients," said Azra Raza, M.D., Director, MDS Program,
St. Vincent's Comprehensive Cancer Center, New York. "These results show
that high sensitivity testing may help physicians detect undiagnosed PNH
in patients with bone marrow failure disorders, and identify those
patients with bone marrow failure who may be more likely to respond to
immunosuppressive therapy."
Dr. Raza is the senior author of a poster titled, "Prevalence of
Paroxysmal Nocturnal Hemoglobinuria (PNH) Cells in Patients with
Myelodysplastic Syndromes (MDS), Aplastic Anemia (AA) or Other Bone
Marrow Failure Syndromes (BMF): Interim Results from the EXPLORE Trial."
The poster will be presented on Saturday, May 30 from 8:00 a.m. to noon
in West Hall C on Level 2 of the Orange County Convention Center in
Orlando, Fla.
Interim results from the EXPLORE trial are based on 5,285 patients with
evidence of bone marrow failure, including 4,433 with MDS, 451 with AA,
and 351 with other bone marrow failure syndromes (including patients
with more than one diagnosis). To eliminate variability in the detection
and reporting of PNH cell populations, a central laboratory employed a
commercially available high-sensitivity flow cytometry test to identify
GPI anchor-deficient PNH red blood cells and white blood cells,
resulting in 0.01% sensitivity. Interim results are as follows:
-
PNH cells were present in 70% of patients with AA, 55% of patients
with MDS, and 55% of patients with other BMF syndromes when tested at
a sensitivity of 0.01% PNH cells.
-
PNH clones of clinical significance (â%¥1% of white blood cells) were
found in 25% of patients with AA (113 of 451), 1% of patients with MDS
(54 of 4,433) and 5% of patients with other BMF syndromes (16 of 351).
-
Among patients with PNH clones of clinical significance, elevated
levels of hemolysis, or red blood cell destruction, were evident in
38% of patients with AA, 44% of patients with MDS, and 69% of patients
with other BMF syndromes. In PNH, excessive hemolysis can lead to
thrombosis, pulmonary hypertension, kidney failure, pain and fatigue
in affected patients.
-
Most patients who tested positive had smaller populations of PNH cells
(< 1% of white blood cells), demonstrating the need to test patients
using flow cytometry with sufficiently high sensitivity capable of
detecting these abnormal cells.
-
PNH cells were identified in patients with all subtypes of MDS as well
as in patients with both severe and non-severe aplastic anemia,
supporting the clinical importance of testing all MDS and AA patients.
Importance of Detecting PNH Cells
Research shows that patients with MDS, AA and other BMF syndromes have a
greater likelihood of having PNH. However, these patients are often
overlooked for PNH testing due to the perceived rarity of PNH cells, and
also because certain symptoms of BMF syndromes overlap with those of
PNH. Importantly, the identification of PNH cells in patients with BMF
syndromes may impact the mode of treatment for the bone marrow disorder,
regardless of the treatment decision regarding the patient's PNH. For
example, studies have suggested that the presence of even a small number
of PNH cells detected by high sensitivity flow cytometry may predict
that the AA or MDS component of patients' disease has a higher
likelihood of a clinically important response to immunosuppressive
therapy (IST). (1,2,3)
Researchers continue to enroll patients with AA in the EXPLORE study,
which is expected to eventually test almost 6,000 patients. When
completed, the results are expected to help define those patients with
bone marrow failure syndromes who should be tested for PNH and how the
test should be conducted.
"A growing number of hematologists and oncologists are interested in
establishing better diagnostic pathways for PNH with the goal of
ensuring timely diagnosis and effective management of this ultra-rare,
debilitating and life-threatening disease," said Leonard Bell, M.D.,
Chief Executive Officer of Alexion Pharmaceuticals, Inc. "The EXPLORE
trial provides valuable data to support this effort and further
establishes the important role of early diagnosis with high sensitivity
flow cytometry in testing patients with bone marrow disorders for the
presence of PNH cells." Alexion has developed and currently markets a
treatment for patients with PNH approved in the U.S., European Union,
Australia, and Canada.
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. (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) It is
estimated that approximately one-third of patients with PNH do not
survive more than five years from the time of diagnosis. (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) More information on PNH is available at www.pnhsource.com.
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(R) (eculizumab) is Alexion's
first marketed product, approved in the U.S. and Europe in 2007, and
Canada and Australia in 2009. 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. 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 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,
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.
1. Wang H, et al. Blood. 2002;100:3897-3902.
2. Sugimori C, et al. Blood. 2006:107:1308-1314.
3. National Comprehensive Cancer Network. Clinical Practice Guidelines
in Oncology: Myelodysplastic Syndromes. V.1.2009. Available at: www.nccn.org
4. 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.
5. Parker C, Omine M, Richards S, et al. Diagnosis and management of
paroxysmal nocturnal hemoglobinuria. Blood. 2005;106
(12):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.
SOURCE: Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Sr. Director, Corporate Communications
or
Media:
Makovsky & Company
Kristie Kuhl, 212-508-9642
or
Investors:
Rx Communications
Rhonda Chiger, 917-322-2569
Copyright Business Wire 2009