Researchers Report Clinical Association Between Type II PNH Cells and Thrombocytopenia
Study Presented at ASH Annual Meeting Highlights Importance of
Identifying Type II PNH Cells and Using High Sensitivity Methods to
Diagnosis PNH Abstract 3015, Poster Board II-991
CHESHIRE, Conn., Dec 06, 2009 (BUSINESS WIRE) -- Alexion
Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced presentation of
data showing that the presence of Type II paroxysmal
nocturnal hemoglobinuria (PNH) cells is correlated with
thrombocytopenia, potentially indicating that patients with Type II
cells experience ongoing platelet consumption and increased thrombosis
risk. The study also highlights the need to identify Type II PNH
cells from both red and white blood cells when diagnosing the disease
and continues to demonstrate the need for high sensitivity flow
cytometry methods.
The data were presented today at the 51st
Annual Meeting of the American Society of Hematology in New Orleans
in a poster session titled, "Identification
and Clinical Significance of Type II Granulocytes Among Patients with
Paroxysmal Nocturnal Hemoglobinuria (PNH) Identified Using
Multiparameter High-Sensitivity Flow Cytometry."
In the study, a large population of patients was tested for the presence
of PNH clones using a high-sensitivity flow cytometry assay, which
identified a notable population of PNH patients with detectable PNH
granulocyte (Gran) clones. In the evaluation of granulocyte markers for
Type II clones by high sensitivity flow cytometry, the FLAER reagent
identified all Type II granulocyte PNH clones while antibodies to
GPI-linked proteins demonstrated less sensitivity.
"Detection of Type II granulocyte PNH cells is clinically important, as
specific identification of PNH red blood cell clones can be confounded
by transfusion or hemolysis," said Mayur K. Movalia, M.D., Associate
Pathologist for Dahl-Chase Diagnostic Services and lead author of the
study. "Further, the observed association of thrombocytopenia and Type
II cells, without detectable differences in other peripheral blood cells
or parameters, suggests that the presence of Type II cells may be an
additional marker for increased thrombotic risk in patients with PNH."
Thrombosis has been observed in PNH patients regardless of the level of
hemolysis. Life-threatening thromboembolism is the most serious
complication of PNH and accounts for 40 to 67 percent of patient deaths.
(1)
"We appreciate the clinical importance of these study results showing a
correlation between the presence of type II PNH cells and
thrombocytopenia in patients with PNH," said Stephen Squinto, Ph.D.,
Executive Vice President and Head of Research and Development at
Alexion. "These data help advance our understanding of PNH and highlight
the importance of using high sensitivity methods as well as evaluating
Type II PNH cells in the diagnostic evaluation of potential PNH
patients."
Clinical Data
Researchers evaluated 2,921 consecutive patient blood samples submitted
for PNH diagnostic testing to distinguish Type I, II and III granulocyte
(Gran) clones. The samples were evaluated with a high-sensitivity flow
cytometry assay for granulocytes including the FLAER reagent and
complement inhibitor and lineage-specific antibodies. (2)
Following evaluation, 216 patient samples had a detectable PNH Gran
clone, of which, clinical information was available for 162 of these
patients. Of these samples, 19 patients demonstrated a distinct Type II
Gran population (median Type II clone size = 7 percent). In 21 percent
of the population, this Type II Gran clone represented >50 percent of
the total (Type II + Type III) PNH cells.
Importantly, the presence of type II PNH granulocytes was associated
with a significant increase in the incidence of thrombocytopenia.
Patients with Type II Gran clones more commonly demonstrated platelet
counts below 100,000 (68% vs. 44%, P=0.05) and showed significantly
lower median platelet counts than patients without Type II Gran clones
(54 x109/L vs. 116x109/L; p=0.01). Patients with
Type II Gran clones had similar peripheral white blood cell, red blood
cell, and absolute neutrophil counts, as well as hemoglobin level (Hgb)
compared to patients without Type II Gran clones, suggesting that
differences in platelet counts are likely not due to differences in
underlying marrow blood cell production, but rather to enhanced platelet
consumption in patients with Type II Gran clones. These data suggest
that the presence of Type II cells may be an additional marker for
increased thrombotic risk in patients with PNH.
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. (3) 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). (4,5) Approximately 10 percent of all patients first
develop symptoms at 21 years of age or younger. (4) 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. (1) It is estimated that approximately
one-third of patients with PNH do not survive more than five years from
the time of diagnosis. (1) 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. (4) 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 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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of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;
333:1253-1258.
2. Movalia M, et al. Identification and Clinical Significance of Type II
Granulocytes Among Patients with Paroxysmal Nocturnal Hemoglobinuria
(PNH) Identified Using Multiparameter High-Sensitivity Flow Cytometry.
Presented at the 51st Annual Meeting of the American Society of
Hematology, December 6, 2009; Poster Board # II-991.
3. 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.
4. Parker C, Omine M, Richards S, et al. Diagnosis and management of
paroxysmal nocturnal hemoglobinuria. Blood. 2005;106
(12):3699-3709.
5. Hill A, Richards S, Hillmen P. Recent developments in the
understanding and management of paroxysmal nocturnal haemoglobinuria. Br
J Haematol. 2007;137:181-92.
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.
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.
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