New Research Presented at EHA Congress Shows That Soliris® Significantly Reduced Hemolysis in Never-Transfused Patients with PNH
Separate Analysis of Patients with PNH and Thrombocytopenia Found
Sustained Platelet Recovery Following Treatment with Soliris
CHESHIRE, Conn., Jun 07, 2009 (BUSINESS WIRE) -- Clinical investigators observed that Soliris(R) (eculizumab), a
first-in-class terminal complement inhibitor developed by Alexion
Pharmaceuticals, Inc. (Nasdaq: ALXN), reduced hemolysis (red blood cell
destruction) and improved symptoms in nine patients with paroxysmal
nocturnal hemoglobinuria (PNH) who had received no blood transfusions
prior to initiating Soliris therapy.
In a separate study of 11 patients with PNH, researchers observed
sustained platelet recovery with Soliris treatment in a subset of seven
patients with thrombocytopenia (reduced platelet levels), indicating a
likely reversal of platelet consumption with Soliris in these
thrombocytopenic PNH patients. These and other data sets were presented
on June 6 and 7 at the European Hematology Association Congress in
Berlin. Soliris is the only therapy approved in the European Union,
United States, Australia and Canada for the treatment of patients with
PNH, an ultra-rare, debilitating, and life-threatening blood disorder.
"All patients with PNH, including those who do not require transfusion
and may appear to be stable, are at increased risk for blood clots,
kidney dysfunction, pulmonary hypertension and disabling fatigue caused
by hemolysis," noted Leonard Bell, M.D., Chief Executive Officer of
Alexion. "Research presented at EHA is a sobering reminder of the
clinical consequences of this progressive, ultra-rare disease. These
data further underscore the clinical impact of Soliris for the treatment
of patients with PNH, and also provide insight into the potential role
of complement inhibition in addressing other complement-mediated
diseases."
Never-Transfused and Minimally Transfused Patients with PNH
Abstract 0581 titled "Efficacy of the Complement Inhibitor Eculizumab in
Paroxysmal Nocturnal Hemoglobinuria Patients Never Transfused," was
presented at a poster session at the EHA Congress on Saturday, June 6 by
Dr. Antonio Risitano, Research Associate at the University of Naples in
Italy.
Published research shows that Soliris reduces hemolysis in patients with
PNH who require minimal transfusions. (1) However, many patients with
PNH do not receive blood transfusions and continue to experience
hemolysis and its clinical consequences. In this analysis, investigators
assessed the safety and efficacy of Soliris in the treatment of nine
patients with PNH who required no transfusions prior to starting Soliris
therapy. These "never-transfused" patients were enrolled in the Italian
Early Access Program with at least one of the following conditions:
severe anemia due to intravascular hemolysis; frequent paroxysmal
crises; severe symptoms due to hemolysis; or thrombosis
(life-threatening blood clots).
All patients experienced a dramatic reduction in hemolysis following
treatment with Soliris for a median of 16 months, as measured by a
median reduction in LDH from 1,500 U/L before treatment to 356 U/L after
treatment (p=0.008). Overall, hemoglobin levels increased significantly
from 9.0 g/dL before treatment to 10.7 g/dL after treatment (p=0.0003),
with a median increase of 2.0 g/dL. The investigator noted that patients
reported a marked improvement in quality of life. No serious adverse
events were reported.
Investigators compared these results to a subset of 21 patients
previously enrolled in eculizumab clinical trials who had received zero
or one transfusion during the year prior to eculizumab treatment. These
patients experienced a significant reduction in hemolysis following six
months of Soliris therapy, with a median reduction in LDH from 2,030 U/L
before treatment to 336 U/L after treatment (p < 0.001). Hemoglobin
levels increased significantly from 9.0 g/dL before treatment to 10.7
g/dL after treatment (p=0.0003), with a median increase of 1.7 g/dL.
Fatigue was also significantly improved (p<0.001).
"PNH is a debilitating and life-threatening disease, even among patients
who do not require blood transfusion," noted Dr. Risitano. "Based on
clinical data, eculizumab therapy inhibited hemolysis in these
never-transfused patients, leading to immediate clinical benefit and
potentially reducing the long-term morbidity and mortality associated
with this ultra-rare disease."
Patients with PNH and Thrombocytopenia
Abstract 0584 titled "Effect of Eculizumab Therapy on Thrombocytopenia
in Patients with Paroxysmal Nocturnal Hemoglobinuria," was presented at
a poster session at the EHA Congress on Saturday, June 6 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.
Dr. Weitz presented additional results from an ongoing prospective study
to measure the effect of Soliris therapy on measures of inflammation and
thrombin generation in patients with PNH. The study uses highly
sensitive laboratory tests to analyze blood samples collected from
patients with PNH prior to treatment with Soliris and prior to each dose
during the following 90 days.
Preliminary results presented at the American Society of Hematology
Annual Meeting in December 2008 found that patients with PNH, only one
of whom had been previously diagnosed with a blood clot, exhibited a
hypercoagulable state (high risk of blood clots) prior to treatment with
Soliris, as indicated by elevated levels of key inflammatory and
pro-thrombotic measures, including D-dimers and thrombin-antithrombin
(TAT) complex. (2)
Among the 11 patients enrolled in this study, seven had thrombocytopenia
with platelet counts below 100 x 109/L (range: 26 to 88 x 109/L)
prior to Soliris treatment. A sustained platelet recovery above 100,000
occurred in four out of seven patients during treatment with Soliris for
periods ranging from two to 20 months. Levels of D-Dimer and TAT were
elevated in all of the patients with thrombocytopenia prior to
treatment, and decreased following Soliris therapy.
"These results suggest that in some patients with PNH, thrombocytopenia
may be due to platelet consumption and not bone marrow failure," said
Dr. Weitz. "The finding that Soliris reduces thrombin-mediated platelet
consumption in these PNH patients may have implications for the
treatment of patients with other complement-mediated diseases
complicated by thrombocytopenia."
Additional Data
The following research was presented during a poster session at the EHA
Annual Meeting on Saturday, June 6:
-
Abstract 0585: "Efficacy of the Terminal Complement Inhibitor
Eculizumab Used Chronically in a Patient with Cold Agglutinin Diseases
(CAD)," Dr. Alexander Röth.
-
Abstract 0587: "Modification of the Standard Eculizumab Dose To
Successfully Manage Intravascular Haemolysis Breakthrough in Patients
with Paroxysmal Nocturnal Hemoglobinuria," Dr. Richard Kelly.
The following research was presented in an oral presentation at the EHA
Annual Meeting on Sunday, June 7:
-
Abstract 1110: "Eculizumab Reduces Pulmonary Hypertension Through
Inhibition of Haemolysis-Associated Nitric Oxide Consumption in
Patients with Paroxysmal Nocturnal Hemoglobinuria," Dr. Anita Hill.
The following research was presented in an oral presentation at the EHA
Annual Meeting on Sunday, June 7:
-
Abstract 1114a: "Successful Pregnancy Outcome in Paroxysmal Nocturnal
Hemoglobinuria on Long Term Eculizumab," Dr. Richard Kelly.
About PNH
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) PNH is an ultra-rare blood disorder that
strikes people of all ages, with an average age of onset in the early
30s. (5) 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. (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. (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 paroxysmal
nocturnal hemoglobinuria (PNH), a rare, debilitating and
life-threatening blood disorder defined by hemolysis, or the destruction
of red blood cells. All four jurisdictions reviewed and approved their
respective marketing applications for Soliris under their priority
review or accelerated assessment procedures, and all four have
designated Soliris as an orphan drug. 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. 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,
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. Bessler M, Schrezenmeier H, MaciejewskiJP, et al. Significant disease
burden in paroxysmal nocturnal hemoglobinuria patients with lower levels
of hemolysis, mild anemia and minimal transfusion: clinical improvement
with eculizumab therapy [abstract]. Blood. 2007; 110 (11): A840.
2. Weitz IC, Ghods M, Rochanda L, et al. Eculizumab therapy results in
rapid and sustained decreases in markers of thrombin generation and
inflammation in patients with PNH [abstract]. Blood.
2008;112:A407.
3. Parker C, Omine M, Richards S, et al. Diagnosis and management of
paroxysmal nocturnal hemoglobinuria. Blood. 2005;106
(12):3699-3709.
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.
5. 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.
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
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