Long-Term Soliris® Treatment Resulted in Sustained Reduction in Hemolysis and Improved Kidney Function in Japanese Patients with PNH
In AEGIS Study Extension Presented at ASH Annual Meeting, Two-Thirds
of Japanese Patients Were Affected by Chronic Kidney Disease at
EnrollmentAbstract 1980, Poster Board I-1002
CHESHIRE, Conn., Dec 05, 2009 (BUSINESS WIRE) -- Alexion
Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced positive data
from the 26-week extension of the AEGIS study, an open-label
registration study examining Soliris(R)
(eculizumab) for the treatment of Japanese patients with paroxysmal
nocturnal hemoglobinuria (PNH). The study showed that after 38 weeks
of Soliris treatment, all patients with chronic kidney disease (CKD), a
clinical consequence of chronic hemolysis, either stabilized or
improved. Other studies have shown that kidney disease accounts for 18
percent of deaths among Japanese patients with PNH. (1) In the studied
patients, Soliris therapy was also associated with a sustained reduction
in hemolysis, which resulted in a further improvement in levels of
fatigue, as well as a maintained improvement in anemia and a reduction
in transfusion requirements.
The data were presented today at the 51st
Annual Meeting of the American Society of Hematology (ASH) in a
poster titled "Chronic
Renal Insufficiency in Japanese Patients with Paroxysmal Nocturnal
Hemoglobinuria (PNH): Improvement with Eculizumab Treatment in the
Long-Term Follow-up of the AEGIS Study."
"Chronic kidney disease is one of the most common and life-threatening
complications of hemolysis among Japanese patients with PNH. In this
extension study, clinical improvements in kidney function with
eculizumab therapy were particularly evident in patients with early
stage kidney disease, which underscores the importance of early
intervention with eculizumab," said Yuzuru Kanakura, M.D., Ph.D.,
Professor of Hematology and Oncology at Osaka University Hospital in
Suita, Japan, and lead author of the study. "We are pleased that
eculizumab continues to show a sustained reduction in hemolysis,
beneficial effects on kidney function, and a significant improvement in
quality of life."
Initial efficacy and safety data from the 12-week AEGIS study were
presented at the ASH meeting in 2008. This 26-week extension study,
which is still ongoing, further evaluated Soliris in Japanese patients
with PNH and allowed for a comparison with the results from the Phase
III, multinational trials conducted in the United States and Europe.
"The long-term data from the AEGIS study continue to be consistent with
those observed in the SHEPHERD and TRIUMPH Phase III clinical trials,
which also showed significant reductions in hemolysis, anemia,
transfusion dependence, and fatigue among patients with PNH in the U.S.
and Europe who were treated with Soliris," said Leonard Bell, M.D.,
Chief Executive Officer of Alexion. "We anticipate that regulatory
authorities in Japan may make a decision on our application for
marketing authorization next year, and we are preparing to make Soliris
available to physicians and patients in Japan in late 2010."
Clinical Data from the AEGIS Extension Study
Twenty-seven Japanese patients entered the extension of the AEGIS study.
Patients received 600 mg of Soliris every 7 days (+/- 2
days) for 4 weeks; 900 mg one week later; then 900 mg every 14 days (+/-
2 days) for a total of 38 weeks of therapy. (2)
Results showed that there was a sustained reduction in intravascular
hemolysis, as measured by lactate dehydrogenase (LDH), through the 38
weeks of treatment. LDH decreased 87% from a median of 1,814 U/L at
baseline to a median of 232 U/L at 38 weeks of treatment (p<0.001).
A significant improvement in chronic kidney disease (CKD) stage was also
seen in Japanese patients on long-term Soliris treatment. Two-thirds
(19/29) of patients enrolled in the AEGIS study demonstrated evidence of
CKD at baseline prior to eculizumab. At week 38, 33% (9/27) of patients
showed improvement in CKD while 67% (18/27) showed no change from
baseline and no patients (0%) worsened (p<0.05). Further, 53% (9/17) of
patients with CKD at baseline demonstrated improvement. Among the 9
patients who showed improvement, 8 had stage 1-2 CKD at baseline and one
had stage 3-5 at baseline.
Soliris treatment continued to appear to be safe and well-tolerated in
treated patients during the initial 26-weeks of the extension study.
Four patients experienced 9 serious adverse events (SAEs); one patient
experienced 4 SAEs that were reported as probably or possibly related to
the drug. Most adverse events (AEs) were mild in severity. The most
frequent AEs were nasopharyngitis (52%), headache (19%), blood alkaline
phosphatase increases (19%) and anemia (11%). No thrombotic events or
meningococcal infections were reported during Soliris treatment.
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. (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 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.
References
1. 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.
2. Kanakura, Y, et al. Chronic Renal Insufficiency in Japanese Patients
with Paroxysmal Nocturnal Hemoglobinuria (PNH): Improvement with
Eculizumab Treatment in the Long-Term Follow-up of the AEGIS Study.
Presented at the 51st Annual Meeting of the American Society of
Hematology, December 5, 2009; Poster Board # I-1002 [Blood 2009;114:1980]
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. 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
Makovsky & Company
Mark Marmur (Media), 609-354-8135
or
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Rhonda Chiger (Investors), 917-322-2569
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