New England Journal of Medicine Publishes Case Reports on the Investigational Use of Soliris® (eculizumab) in Patients with Atypical Hemolytic Uremic Syndrome (aHUS)
Alexion To Begin Clinical Trials of Soliris(R)
in aHUS Patients
CHESHIRE, Conn., Jan 29, 2009 (BUSINESS WIRE) -- Two separate case reports published today in the New England Journal
of Medicine (NEJM) examine the investigational use of Soliris
(R) (eculizumab), a terminal complement inhibitor developed by
Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN), in patients with a rare
and severe inflammatory disease called atypical Hemolytic Uremic
Syndrome (aHUS). In both cases, physicians observed a significant
reduction in the destruction of red blood cells, reduced platelet
consumption and improved kidney function following Soliris therapy.
Separately, Alexion announced today that it is currently initiating
clinical trials of eculizumab in patients with aHUS. Soliris is approved
in the United States, European Union, and Canada for the treatment of
patients with paroxysmal nocturnal hemoglobinuria (PNH).
Atypical Hemolytic Uremic Syndrome is characterized by hemolysis,
thrombocytopenia and clotting of blood vessels (microangiopathy),
particularly in the kidney and brain, often progressing to end-stage
kidney disease. Like PNH, aHUS is caused by a deficiency in normally
occurring complement inhibitors. Typically, patients with aHUS have
genetic mutations in one of several complement inhibitor proteins that
lead to uncontrolled complement activation. Excessive complement
activation may contribute to severe inflammation of the blood vessels
and blood clotting through the activation of white blood cells,
platelets, and the endothelial cell lining of blood vessels. (1)
The prognosis for patients with aHUS is poor. Approximately 70% of
patients with the most common mutation experience chronic renal
insufficiency, chronic dialysis, or death by one year after the first
clinical episode. (2) Following kidney transplantation, recurrent aHUS
causes kidney transplant failure in approximately 62 - 88% of patients.
(3)
Case Reports
In a case report submitted to the NEJM by Ralph A. Gruppo, M.D.,
Director of the Comprehensive Hemophilia and Thrombosis Center at the
Cincinnati Children's Hospital Medical Center, an 18-month-old infant
was admitted to the hospital following a fourth clinically severe
relapse of congenital aHUS. During this episode, the patient did not
respond to daily plasmapheresis, a procedure whereby proteins are
removed from the blood by circulating the patient's blood through a
machine. When the patient's condition deteriorated further, the
physician administered Soliris. Complete blockade of terminal complement
was observed in this patient, and hematologic and renal improvement
began within 48 hours after initiation of treatment. Plasmapheresis was
discontinued within the first week of eculizumab treatment and clinical
remission was sustained throughout the 60 day observation period. The
report further notes that eculizumab therapy is ongoing for over four
months, to date, with sustained disease remission and no further plasma
therapy intervention.
"It is well known that aHUS is a devastating disease without effective
treatment options," explained Dr. Gruppo, lead author of the report.
"Further, after clinical worsening, there may be virtually nothing a
physician can do to prevent further kidney damage and eventual kidney
failure. Based on this initial and very limited experience, further
studies of terminal complement inhibition with eculizumab are warranted."
In a second case reported in the same issue of the NEJM by Dr. Jens
Nuernberger of the Department of Nephrology at University Duisburg-Essen
in Essen, Germany, a 37-year-old woman with a history of kidney failure
due to aHUS and loss of her first kidney transplant due to recurrent
aHUS, was admitted to the hospital with progressive and severe aHUS
shortly after her second kidney transplant. The patient's aHUS condition
continued to clinically worsen despite extensive plasma treatments,
indicating a high probability that the second kidney transplant would
fail. After the administration of eculizumab, hemolysis quickly
resolved, platelet count rebounded and kidney transplant function
recovered. The patient's renal graft function has remained stable.
Eculizumab appeared to be well tolerated in these two patients, with
safety observations that have been consistent with those reported from
controlled trials with eculizumab in patients with PNH.
"There is a profound need to improve the management of aHUS. We are
encouraged by the initial clinical experience with eculizumab in a very
limited number of aHUS patients, and we are undertaking prospective
clinical trials to investigate the role of complement inhibition in this
condition," said Leonard Bell, M.D., Chief Executive Officer of Alexion.
Upcoming Clinical Studies
Alexion is currently initiating four prospective, open-label clinical
studies of eculizumab as a treatment for patients with aHUS in North
America and multiple European countries: two studies of patients who are
plasma therapy sensitive (one in adults and one in adolescents) and two
studies of patients who are plasma therapy resistant (one in adults and
one in adolescents). Information on the trials can be requested by
e-mail using the address clinicaltrials@alxn.com,
or by visiting the Alexion website at www.alexionpharma.com
and clicking on the clinical trials link. The trials also will be posted
to the www.clinicaltrials.gov
website maintained by the U.S. National Institutes of Health.
About Soliris
Soliris was approved in March 2007 by the U.S. Food and Drug
Administration (FDA) as the first treatment for PNH, a rare,
debilitating and life-threatening blood disorder defined by hemolysis,
or the destruction of red blood cells. In June 2007 and January 2009,
respectively, the European Commission (EC) and Health Canada also
approved the use of Soliris for the treatment of patients with PNH.
Soliris is the first therapy approved in the U.S., Europe and Canada for
the treatment of PNH and was the first medicinal product to receive EC
approval under the EMEA Accelerated Assessment Procedure. Soliris is not
approved in the U.S., Europe, Canada or elsewhere for the treatment of
atypical Hemolytic Uremic Syndrome (aHUS).
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.
Please see full U.S. prescribing information at www.soliris.net.
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 diseases, cancer and autoimmune disorders. In
March 2007, the FDA granted marketing approval for Alexion's first
product, Soliris, for all patients with PNH, and Alexion began
commercial sale of Soliris in the U.S. during April 2007. In June 2007,
the EC granted marketing approval for Soliris in the European Union for
all patients with PNH, and in January 2009, Health Canada granted
marketing approval in Canada for all patients with PNH. 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 or published case reports 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 September 30, 2008, 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) Stahl A, Vaziri-Sani F, Heinen S, Kristoffersson A-C, Gydell K-H,
Raafat R, Gutierrez A, Beringer O, Zipfel PF, and Karpman D. Factor H
dysfunction in patients with atypical hemolytic uremic syndrome
contributes to complement deposition on platelets and their activation. Blood.
2008;111:5307-5315
(2) Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F,
Bettinaglio P, et al. Genetics of HUS: the impact of MCP, CFH, and IF
mutations on clinical presentation, response to treatment, and outcome. Blood.
2006 Aug 15;108(4):1267-79).
(3) Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical
hemolytic uremic syndrome in children. Pediatr Nephrol. 2008
Nov;23(11):1957-72.
SOURCE: Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Sr. Director Corporate Communications
or
Makovsky & Company
Kristie Kuhl (Media), 212-508-9642
or
Rx Communications
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