Study Evaluating Eculizumab (Soliris®) in Preventing Antibody-Mediated
Rejection (AMR) in Kidney Transplant Recipients Presented at the European
Society for Organ Transplantation (ESOT) Annual Congress
– Preliminary Data Show Potential for Effective Prophylaxis Against Early
Acute AMR in Deceased-Donor Kidney Transplant Recipients Highly Sensitized to
Their Donors –
CHESHIRE, Conn. -- September 10, 2013
Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that researchers
have presented preliminary data from a single-arm Phase 2 study of eculizumab
(Soliris^®) as an investigational therapy to prevent acute antibody-mediated
rejection (AMR) in sensitized deceased-donor kidney transplant recipients. The
composite primary endpoint was the nine-week occurrence of
post-transplantation treatment failure, which occurred in 10.6% of the 47
patients reported today, including a 6.4% rate of AMR^1 compared to an
expected 30% rate of AMR^2 in this highly sensitized population of kidney
transplant recipients. The data were presented today in an oral presentation
at the 2013 annual congress of the European Society for Organ Transplantation
(ESOT) in Vienna, Austria.
Acute AMR can lead to severe kidney allograft damage resulting in rapid loss
of function and possible loss of the transplanted kidney, which makes AMR a
significant clinical barrier to transplantation in sensitized patients.^3
Research suggests that uncontrolled activation of complement, triggered by the
binding of donor-specific antibodies (DSAs) to their target proteins
(antigens) of the donor kidney, may be the primary reason for acute AMR in
kidney transplant recipients who are sensitized, or have DSAs, to their
donors.^3,4 Prophylaxis with a terminal complement inhibitor, such as
eculizumab, is thus considered a potential strategy to prevent acute AMR.
There are no approved treatments for the prevention of acute AMR.
“Approximately 30% of kidney transplant candidates on waiting lists are
sensitized, or have antibodies, to potential donors. Because conventional
immunosuppressive therapies are ineffective for the prevention of AMR,
sensitized patients often have to wait years for a kidney suitable for
transplantation. Thus, AMR has emerged as a significant, long-standing
clinical problem in transplantation,” said Denis Glotz, M.D., Ph.D., Chief of
the Department of Nephrology and Transplantation at Saint-Louis Hospital in
Paris, France. “The data from this study suggest that eculizumab may be an
effective prophylaxis against acute AMR in kidney recipients with preexisting
antibodies against their donor.”
“This study suggests that eculizumab, by inhibiting the activation of terminal
complement, could be effective in preventing acute AMR, which is a severe and
life-threatening complication in sensitized patients undergoing kidney
transplantation,” said Martin Mackay, Ph.D., Executive Vice President and
Global Head of R&D at Alexion. “We are encouraged by the data presented today
from this deceased-donor study, and also continue to enroll patients in our
multi-national living-donor transplant trial in patients at elevated risk of
Eculizumab is approved in over 40 countries as a treatment for patients with
paroxysmal nocturnal hemoglobinuria (PNH) and in the United States, European
Union and other countries for patients with atypical hemolytic uremic syndrome
(aHUS). PNH and aHUS are both debilitating and life-threatening ultra-rare
disorders caused by chronic, uncontrolled complement activation. Eculizumab is
not approved for the prevention of AMR in any country and was used in the
reported study on an investigational basis.
About the Study
Nine-week preliminary results were presented from an open-label, single-arm,
multicenter Phase 2 trial in which 47 sensitized recipients of kidneys from
deceased donors were treated with eculizumab. The mean age of the study
participants was 50 years (range: 29-70).^1
The study’s primary efficacy composite endpoint was post-transplantation
treatment failure rate at Week 9, defined by biopsy-proven AMR, graft loss,
patient death, and/or loss to follow-up. Preliminary results presented today
are for the primary endpoint modified with utilization of local laboratory
data (the pre-specified primary endpoint uses central lab data). At Week 9, 5
patients (10.6%; 95% confidence interval [CI]: 3.5%, 23.1%) were considered
treatment failures, of which 3 (6.4%) had acute AMR. The three most common
serious adverse events from Weeks 1 to 11 were complications of the
transplanted kidney (12.8%), transplant rejection (8.5%), and acute renal
failure (8.5%). One patient (2%) in the study died due to a post-operative
myocardial infarction deemed not related to eculizumab.^1
About Acute Antibody-Mediated Rejection (AMR)
Acute antibody-mediated rejection (AMR) is a severe and potentially
life-threatening condition that can lead to severe kidney allograft damage
resulting in rapid loss of function and possible loss of the transplanted
kidney. Patients who are sensitized (have high levels of
donor-specific-antibodies or DSAs) are at high risk for developing acute AMR,
may have difficulty finding a viable donor organ, and therefore may never
become eligible for transplantation. The development of acute AMR is believed
to be primarily a result of uncontrolled complement activation caused by DSAs,
which in turn frequently results in allograft damage and dysfunction,
potential graft loss, and/or shortened graft survival.
While solid organ transplantation is the most effective form of therapy for
the treatment of patients with end-stage renal disease (ESRD),^5 concern about
the consequences of AMR remains a significant obstacle to transplantation, as
it results in significant delays for affected patients to access a suitable
transplant. Overall, ESRD patients on dialysis have a very high mortality rate
since approximately 65% of these patients die within 5 years of commencing
dialysis.^6 Additionally, approximately one-third of patients on the kidney
transplant waiting list are sensitized to their potential donors^7 and
historically, approximately 30% of this highly sensitized population has
developed AMR.^2 A therapy that prevents acute AMR is critically important for
sensitized patients with ESRD. Currently, there are no approved therapies for
the prevention of acute AMR.
Soliris is a first-in-class terminal complement inhibitor developed from the
laboratory through regulatory approval and commercialization by Alexion.
Soliris is approved in the United States (US), European Union (EU) and other
countries as the first and only treatment for aHUS patients. Soliris is
indicated to inhibit complement-mediated TMA. Soliris is not indicated for the
treatment of patients with Shiga toxin E. coli-related hemolytic uremic
syndrome (STEC-HUS). Alexion is evaluating the safety and efficacy of Soliris
for the treatment of patients with STEC-HUS.
Soliris also is approved in the US, EU, Japan and other countries as the first
and only treatment for patients with paroxysmal nocturnal hemoglobinuria
(PNH), a debilitating, ultra-rare and life-threatening blood disorder
characterized by complement-mediated hemolysis (destruction of red blood
cells). Soliris is indicated to reduce hemolysis.
Alexion's breakthrough approach in terminal complement inhibition has received
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
More information, including the full prescribing information on Soliris, is
available at www.soliris.net.
Important Safety Information
The US product label for Soliris includes a boxed warning: "Life-threatening
and fatal meningococcal infections have occurred in patients treated with
Soliris. Meningococcal infection may become rapidly life-threatening or fatal
if not recognized and treated early. Comply with the most current Advisory
Committee on Immunization Practices (ACIP) recommendations for meningococcal
vaccination in patients with complement deficiencies. Immunize patients with a
meningococcal vaccine at least 2 weeks prior to administering the first dose
of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of
developing a meningococcal infection. (See Serious Meningococcal Infections
(5.1) for additional guidance on the management of meningococcal infection.)
Monitor patients for early signs of meningococcal infections and evaluate
immediately if infection is suspected. Soliris is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy (REMS).
Under the Soliris REMS, prescribers must enroll in the program. Enrollment in
the Soliris REMS program and additional information are available by
telephone: 1-888-soliris (1-888-765-4747)."
In patients with PNH, the most frequently reported adverse events observed
with Soliris treatment in clinical studies were headache, nasopharyngitis
(runny nose), back pain and nausea. Soliris treatment of patients with PNH
should not alter anticoagulant management because the effect of withdrawal of
anticoagulant therapy during Soliris treatment has not been established. In
patients with aHUS, the most frequently reported adverse events observed with
Soliris treatment in clinical studies were hypertension, upper respiratory
tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract
infection, and leukopenia. Please see full prescribing information for
Soliris, including boxed WARNING regarding risk of serious meningococcal
Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on
serving patients with severe and ultra-rare disorders through the innovation,
development and commercialization of life-transforming therapeutic products.
Alexion is the global leader in complement inhibition and has developed and
markets Soliris® (eculizumab) as a treatment for patients with PNH and aHUS,
two debilitating, ultra-rare and life-threatening disorders caused by chronic
uncontrolled complement activation. Soliris is currently approved in more than
40 countries for the treatment of PNH, and in the United States and European
Union for the treatment of aHUS. Alexion is evaluating other potential
indications for Soliris and is developing four other highly innovative
biotechnology product candidates, which are being investigated across
additional severe and ultra-rare disorders beyond PNH and aHUS. 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, regulatory and commercial
milestones and potential health and medical benefits of Soliris® (eculizumab)
for the prevention of antibody mediated rejection (AMR) in kidney transplant
recipients. 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, 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 June 30, 2013 and in our other filings with the US
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 Glotz D, Legendre C, Manook M, et al. Eculizumab decreases early
antibody-mediated rejection in sensitized deceased donor kidney transplant
patients. Presented at the 2013 Congress of the European Society for Organ
Transplantation (ESOT), Vienna, Austria, September 10, 2013.
^2 LeFaucher C, Loupy A, Hill GS, et al. Preexisting donor-specific HLA
antibodies predict outcome in kidney transplantation. J Am Soc Nephrol.
^3 Takemoto SK, Zeevi A, Feng S, et al. National conference to assess
antibody-mediated rejection in solid organ transplantation. Am J Transplant.
^4 Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in
acute humoral renal allograft rejection: diagnostic significance of C4d
deposits in peritubular capillaries.J Am Soc Nephrol. 1999;10(10):2208-14.
^5 Russell JD, Beecroft ML, Ludwin D, Churchill DN. The quality of life in
renal transplantation—a prospective study. Transplantation 1992;54(4):656-60.
^6 Kidney disease statistics for the United States. US Department of Health &
Human Services, National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), National Kidney and Urologic Diseases Information
Clearinghouse (NKUDIC).NIH Publication No. 12–3895; 2012.
^7 About CPRA for Professionals. US Department of Health & Human Services,
Organ Procurement and Transplantation Network.
Accessed September 9, 2013.
Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Executive Director, Corporate Communications
Alexion Pharmaceuticals, Inc.
Kim Diamond, 203-439-9600
Senior Director, Corporate Communications
Rhonda Chiger, 917-322-2569
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