Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) announced today that a
Phase 2 clinical study investigating Soliris® (eculizumab) as a
treatment for patients with atypical Hemolytic Uremic Syndrome (aHUS)
who are resistant to plasma therapy met primary and key secondary
endpoints with high levels of statistical and clinical significance,
according to results presented today at the American Society of
Nephrology (ASN) annual meeting in Denver. The new data are consistent
with an earlier interim analysis contained in the abstract of today's
presentation and published online by ASN on October 20, 2010. Soliris is
a first-in-class terminal complement inhibitor discovered and developed
aHUS is an ultra-rare, chronic and life-threatening disease in which
uncontrolled complement activation causes blood clots in small blood
vessels throughout the body (thrombotic microangiopathy, or TMA) leading
to kidney failure, stroke, heart attack and death.1,2,3 Because aHUS is
a genetic disease, patients have a life-long risk of sudden and severe
complications of uncontrolled complement activation. Approximately 60%
of patients with aHUS require dialysis, undergo a kidney transplant, or
die within one year of diagnosis.4
Patients Resistant to Plasma Therapy
In an oral presentation today, researchers reported final data from a
Phase 2 study of eculizumab in patients with aHUS who were resistant or
intolerant to plasma therapy.5 This analysis included 17 adolescent and
adult patients who received eculizumab therapy for 26 weeks. The
prospective primary endpoint was the change in platelet count from
baseline, a measure of TMA, at 26 weeks. Key prospective secondary
endpoints included TMA event-free status (defined as at least 12
consecutive weeks of stable or increasing platelet counts, absence of
plasma therapy, and no new dialysis), improvements in chronic kidney
disease (CKD) stage, and change in quality of life.
Improvement in Platelet Count: A Measure of TMA Reduction
The primary endpoint of the study, change in platelet count, increased
significantly through 26 weeks of treatment compared to baseline
(p<0.0001) and was increased 96 ± 21 x109/L at 26 weeks of treatment
with eculizumab. Researchers reported that following the first infusion
of eculizumab, platelet count increased significantly at Day 7 (p=0.02).
A key secondary endpoint, TMA event-free status, was achieved in 88% of
patients (15 of 17; 95% CI 64-100).
Improvement in Kidney Function
Researchers reported significant improvement in kidney function with
sustained eculizumab therapy over the 26-week dosing period. Estimated
glomerular filtration rate (eGFR), a standard measure of kidney
function, increased sufficiently to result in an improvement of at least
one stage in CKD in 65% of patients (11 of 17, 95% CI 33-82), and eGFR
increased less than one CKD stage in four additional patients. Of the
seven patients who received dialysis before entering the study, five
became dialysis-free following treatment with eculizumab and remained so
for the entire 26 weeks.
Improvement in Quality of Life Measures
Quality of life as measured by the summary index of the EuroQol 5D
improved significantly through 26 weeks. The improvement was highly
statistically significant compared to baseline (p<0.0001) and was
improved 0.33 ± 0.09 at 26 weeks which was more than five times the
level generally considered to be a clinically meaningful change.6
All reported study results were similar for patients with and without
complement regulatory protein mutations or auto-antibodies. Eculizumab
was well tolerated in the study, and all patients remain alive. There
were no cases of meningococcal infection in the trial. The most frequent
adverse events were anemia, headache, diarrhea and vomiting. Two
patients withdrew from the study; one patient was withdrawn after it was
subsequently determined that the patient met an exclusion criterion and
one patient withdrew from the study due to an adverse event deemed
unrelated to eculizumab.
"These ground-breaking results show that eculizumab significantly
increased platelets and reduced the life-threatening blood clot process
that caused severe damage to the kidney and other organs in these
patients with aHUS," said Christophe Legendre, M.D., a study
investigator and professor of nephrology at University Rene
Descartes-Hôpital Necker in Paris. "The stabilization and improvement of
kidney function observed in this study is particularly meaningful
because these patients are resistant to plasma therapy, one of the
current management strategies for aHUS."
Patients on Plasma Therapy Chronically
In a poster session yesterday, researchers presented interim results
from a separate Phase 2 study of 20 adult and adolescent patients with
aHUS who were receiving plasma therapy chronically prior to starting
treatment with eculizumab.7 These interim results were the same as
previously reported. The prospective primary endpoint in this study was
TMA event-free status, which was achieved by a significant 87% of
patients in the interim 12-week analysis of 15 patients (13 of 15; 95%
CI 60-98). The analysis also met a key prospective secondary endpoint:
none of the patients treated with eculizumab required TMA intervention.
"aHUS is a devastating disease and patients are chronically at risk for
disease progression including sudden onset of stroke, heart attack,
kidney failure and death, even if they are treated frequently with
currently available interventions," said Petra Muus, M.D., Ph.D., study
investigator and associate professor of hematology at Radboud University
Medical Center in the Netherlands. "These findings show that studied
patients demonstrated an immediate response and sustained efficacy with
eculizumab, giving the aHUS community hope for reducing the need for new
dialysis and plasma therapy."
Eculizumab appeared to be well tolerated in the study. The most frequent
adverse events were diarrhea, nausea, headache and hypertension (all
mild to moderate).
"The results from these Phase 2 studies suggest that it may be possible
to change the course of aHUS by targeting chronic uncontrolled
complement activation," said Leonard Bell, M.D., Chief Executive Officer
of Alexion. "The significant increase in platelet count, reduction in
TMA, restored kidney function, and improved quality of life reported
today indicates that eculizumab may have the potential to transform the
lives of patients with this devastating disease and their families. We
continue to advance this important program."
Alexion has commenced a Phase 2, open-label, single-arm, multi-center
study of eculizumab in pediatric patients with aHUS in the United
States, European Union and Canada. Information about the trial is posted
Identifier Number NCT01193348. Physicians and families who are
interested in participating in this clinical trial can learn more by
contacting Alexion by e-mail at email@example.com,
or by visiting the Alexion website at www.alexionpharma.com
and clicking on the clinical trials link.
aHUS is a chronic, ultra-rare disease characterized by thrombotic
microangiopathy (TMA), the formation of blood clots in small blood
vessels throughout the body, causing a reduction in platelet count
(thrombocytopenia) and life-threatening damage to the kidney, brain,
heart and other vital organs.1-3 Approximately 60 percent of patients
with aHUS require dialysis or a kidney transplant or die within a year
of diagnosis, despite currently available care.4 The majority of
patients with aHUS who receive a kidney transplant experience severe
complications of the disease, and more than 90 percent of these patients
experience failure of the donor kidney.8
aHUS is a progressive disease caused by uncontrolled activation of the
complement system due to genetic deficiency in complement regulatory
genes. With genetic deficiency of naturally occurring complement
inhibitors, patients experience life-long uncontrolled activation of the
complement system, causing ongoing inflammation and blood clots in vital
organs.9,10 In patients with aHUS, uncontrolled complement activation
results in an ongoing risk of sudden and catastrophic life-threatening
Soliris is not approved for the treatment of patients with aHUS and is
being provided to patients in clinical studies on an investigational
basis. Soliris has been approved by the healthcare authorities in the
United States, European Union, Japan and other countries as the first
treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH), a
rare, debilitating and life-threatening blood disorder defined by
hemolysis, or the destruction of red blood cells. Prior to these
approvals, there was no therapy specifically available for the treatment
of PNH. Soliris is a first-in-class terminal complement inhibitor
developed from the laboratory through regulatory approval and
commercialization by Alexion.
Patients with PNH in more than 20 countries now have access to Soliris
therapy through national or private healthcare providers. As the first
terminal complement inhibitor to be approved in countries around the
world for any indication, Soliris represents a long-sought breakthrough
in medical innovation. Alexion's innovative approach to complement
inhibition has received some of the pharmaceutical industry's highest
honors: the 2008 Prix Galien USA Award for Best Biotechnology Product
with broad implications for future biomedical research, and the 2009
Prix Galien France Award in the category of Drugs for Rare Diseases.
More information on Soliris is available at www.soliris.net.
Important Safety Information
Soliris is generally well tolerated in patients with PNH. The most
frequent adverse events observed in clinical studies of patients with
PNH were headache, nasopharyngitis (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 PNH 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
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, other
inflammatory disorders, and cancer. 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.
Safe Harbor Statement
This news release contains forward-looking statements, including
statements related to anticipated clinical development milestones and
potential health and medical benefits of Soliris (eculizumab) for the
potential treatment of patients with aHUS. 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 for its current or potential new
indications, 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, 2010, 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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Pharmaceuticals Corporate Website 2010 September 24 Available from: URL: http://www.alexionpharma.com/RandD/Soliris%20In%20Other/kidney%20disorders.aspx#A1
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