Soliris® (eculizumab) Inhibits TMA and Improves Renal Function in Pediatric and Adult Patients with atypical Hemolytic Uremic

  Soliris®(eculizumab) Inhibits TMA and Improves Renal Function in Pediatric
  and Adult Patients with atypical Hemolytic Uremic Syndrome (aHUS)

–New Data from the Largest Prospective Trial of Adult Patients with aHUS and
First Prospective Trial in Pediatric Patients with aHUS Confirm the Safety and
                        Efficacy Profile of Soliris --

  –ASN Meeting Also Features Three-year Update Data Highlighting Long-term
         Benefits of Chronic Soliris Therapy in Patients with aHUS–

Business Wire

CHESHIRE, Conn. -- November 9, 2013

Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN) today announced that researchers
presented data from four clinical trials, all demonstrating the clinical
benefits of Soliris^®(eculizumab) for the treatment of atypical hemolytic
uremic syndrome (aHUS), a genetic, chronic, ultra-rare disease associated with
vital organ failure and premature death. Soliris is the first and only
approved safe and effective treatment for pediatric and adult patients with
aHUS. In two large, prospective, multinational studies, Soliris inhibited
systemic complement-mediated thrombotic microangiopathy (TMA, the formation of
blood clots in small blood vessels throughout the body) and improved renal
function in both pediatric and adult patients with aHUS.^1,2 The data were
presented at Kidney Week 2013, the annual meeting of the American Society of
Nephrology (ASN) in Atlanta.

The ASN meeting also featured the presentation of three-year update data from
two pivotal Phase 2 extension studies that highlighted the long-term benefits
of Soliris therapy in patients with aHUS. In these studies, ongoing Soliris
treatment at the three-year update was associated with sustained inhibition of
complement-mediated TMA, as indicated by stabilization or continued
improvement in key hematologic and renal endpoints, and quality of
life.^3,4Additionally, investigators presented initial characteristics from
patients enrolled in a global aHUS Registry, which is prospectively collecting
information to enhance understanding of the disease process in order to help
optimize care and improve quality of life for patients with aHUS.^5

aHUS is an ultra-rare, life-threatening, chronic genetic disease that can
progressively damage vital organs, leading to stroke, heart attack, kidney
failure, and death.^6 The morbidities and premature mortality in aHUS are
caused by chronic, uncontrolled activation of the complement system, resulting
in systemicTMA.^7,8Soliris, a first-in-class terminal complement inhibitor,
specifically targets uncontrolled complement activation, and is the first and
only approved treatment for patients with aHUS in the United States, European
Union, Japan and other countries.

“Results from four prospective studies demonstrate a significant and sustained
inhibition of complement-mediated TMA with Soliris treatment and support the
chronic use of Soliris in pediatric and adult patients with aHUS,” said
Leonard Bell, Chief Executive Officer of Alexion. “These studies further
underscore the rationale for initiating Soliris therapy at the time of
clinical diagnosis of aHUS and chronic treatment of patients to achieve
optimal outcomes.”

Soliris in Pediatric Patients with aHUS (Abstract SA-PO0849)

In a poster presentation today, researchers presented positive results from
the first prospective trial of Soliris in pediatric patients with aHUS, which
follows the previously presented positive results of a retrospective study in
pediatric patients with aHUS.^9 This open-label, prospective, single-arm,
multinational trial enrolled a heterogeneous population of patients who were
>1 month old and <18 years of age. It included 22 pediatric patients with
aHUS, of whom 16 (73%) were newly diagnosed. Prior PE/PI was not required for
inclusion in the study. Most patients enrolled in the study (12/22, 55%)
received Soliris as their first aHUS specific treatment and had not received
plasma exchange or infusion (PE/PI) therapy prior to Soliris therapy. Two
patients (9%) had received a prior kidney transplant. The primary endpoint of
the study was the proportion of patients with a complete TMA response, defined
as platelet count normalization, lactate dehydrogenase (LDH) normalization,
and ≥25% improvement in serum creatinine from baseline, during 26 weeks of
treatment.^1

In the study, the median time from current manifestation of aHUS to first dose
of Soliris was six days. Nineteen patients (86%) completed the initial 26
weeks of Soliris therapy, and 14 of 22 patients (64%) achieved the study’s
primary endpoint of complete TMA response at 26 weeks, which required
significant improvement in renal function (≥25% decrease in creatinine).
Platelet count normalization was achieved in 21 of the 22 patients (95%); the
median time to platelet count normalization was seven days and the mean
improvement in platelet count from baseline was 164 x10^9/L (p<0.0001).
Hematologic normalization was observed in 18 of 22 patients (82%). Of the 10
patients on PE/PI at baseline, all (100%) discontinued by the end of the
26-week study.^1

In terms of renal parameters, the mean estimated glomerular filtration rate
(eGFR) increase from baseline was 64 mL/min/1.73m^2 (P<0.001) and 19 patients
(86%) achieved an improvement in eGFR from baseline of at least 15
mL/min/1.73m^2 after 26 weeks. By Week 26, 16 patients (73%) had experienced
at least a 25% decrease from baseline in serum creatinine. Importantly, 9 of
11 patients (82%) who were on dialysis at baseline discontinued dialysis for
the duration of the study and all 12 patients who were not on dialysis at
baseline continued dialysis-free through 26 weeks.^1

“This was the first prospective study of pediatric patients with aHUS, and
demonstrated that chronic Soliris treatment led to rapid and sustained
improvement in platelet counts and significant improvement in kidney function,
including discontinuation of dialysis,” said Larry Greenbaum, M.D., Ph.D.,
Director of Pediatric Nephrology at Emory University and Children's Healthcare
of Atlanta.^10 “The safety and efficacy demonstrated in this prospective trial
confirm the results observed in the previous retrospective pediatric study as
well as the published Phase 2 prospective adult trials, and support the
recommendation of Soliris as a first-line treatment in children with aHUS.”

Soliris was generally well tolerated in the study. The most common adverse
events (AEs) were fever (50%) and cough (36%). One patient had a human
anti-human antibody response, and continued chronic Soliris treatment without
apparent adverse effect. There were no meningococcal infections and no deaths
during the 26-week study.^1

Soliris in Adult Patients with aHUS (Abstract FR-OR057)

In an oral presentation on November 8, researchers presented positive new data
from the largest prospective trial of Soliris in adult patients with aHUS.
This open-label, single-arm, multinational trial enrolled 41 adult patients
with aHUS representing a broad patient population. Prior PE/PI was not
required for inclusion in the study, and the median time from aHUS
manifestation to first dose of Soliris was approximately 2 weeks. Thirty of 41
patients (73%) in the study were newly diagnosed, six patients (15%) had no
PE/PI during the current clinical manifestation, 24 patients (59%) were on
dialysis at baseline, nine patients (22%) had a prior kidney transplant, and
20 patients (49%) had an identified complement factor mutation. All endpoints
were evaluated at 26 weeks of treatment in an intent-to-treat analysis, and 38
(93%) of enrolled patients completed the 26-week study period. The primary
endpoint of the study was the proportion of patients with complete TMA
response, as measured by platelet count normalization, LDH normalization and
preservation of renal function (<25% increase in serum creatinine from
baseline), at 26 weeks.^2

The study met its primary endpoint, with 30 of 41 patients (73%) achieving a
complete TMA response at 26 weeks. Forty of 41 patients (98%) achieved
platelet count normalization (≥150 x10^9/L) by week 26, and the mean increase
in platelet count from baseline was 135x10^9/L (P<0.0001), demonstrating
inhibition of TMA.^2

Soliris significantly improved renal function with a mean increase in eGFR
from baseline of 29 mL/min/1.73m^2 (P<0.0001). Most importantly, of the 24
patients who were on dialysis at baseline, 20 patients (83%) discontinued
dialysis by week 26.^2

“This is the largest study in aHUS and the results confirm those from previous
prospective trials, in which ongoing Soliris treatment led to sustained
inhibition of complement-mediated TMA, rapid and sustained improvements in
hematological parameters, and continued, on-going improvement in renal
function in adult patients with aHUS,” ^ said Fadi Fakhouri, M.D., Ph.D.,
Centre Hospitalier Universitaire de Nantes, Nantes, France.^11 “Results from
this study also support the recent guidelines recommending immediate treatment
with Soliris in adults with aHUS once an unequivocal diagnosis has been made.”

Soliris was generally well tolerated in the study. The most common AEs were
headache (37%), diarrhea (32%) and peripheral edema (22%). There were two
cases of meningococcal infections; both patients recovered, with one patient
continuing on Soliris therapy and one discontinuing therapy with subsequent
deterioration of renal function that necessitated dialysis support. There were
no deaths in the study.^2

Soliris in aHUS Patients with a Long Duration of Disease and Chronic Kidney
Damage (Previously Receiving Prolonged PE/PI): Three-year Update (Abstract
SA-PO850)

In a poster presentation today, researchers presented findings from a
three-year update of a prospective, open-label, single-arm Phase 2 trial of
Soliris in 20 adult and adolescent patients with a long duration of aHUS and
chronic kidney disease (CKD) who were undergoing prolonged PE/PI before
starting treatment with Soliris. Patients had been diagnosed with aHUS a
median of 48 months prior to starting the study. Twenty patients were enrolled
in the initial study and received Soliris for 26 weeks. Nineteen of the 20
patients continued into a long-term extension phase; 16 patients were treated
for 30 months or more and 10 patients remained enrolled in the trial at 3
years. Patients were evaluated for a median duration of 156 weeks. The
co-primary endpoints were TMA event-free status and hematologic
normalization.^3

According to investigators, in aHUS patients with long disease duration and
CKD, long-term treatment with Soliris led to improvements in hematologic and
renal function over 3 years. Treatment with Soliris resulted in achievement of
TMA event-free status (at least 12 consecutive weeks of stable platelet count,
no PE/PI, and no new dialysis) and hematologic normalization in most patients
by 3 years. By the 3-year update, 19 of 20 patients (95%) had achieved TMA
event-free status and 18 of 20 (90%) had achieved hematologic normalization.
Significant improvements in eGFR were observed by week 4 (P<0.01).
Additionally, Soliris treatment maintained long-term improvement in patients’
quality of life, as measured by the EuroQoL5D (EQ-5D) scale, at 3 years
(P=0.0001). Soliris therapy was safe and there were no meningococcal
infections in patients over 3 years of treatment.^3

“These data indicate that significant and time-dependent improvement in kidney
function can be obtained with long-term eculizumab therapy, even in aHUS
patients with a history of chronic kidney damage," stated Yahsou Delmas, M.D.,
Ph.D., at Nephrology Unit, Clearing University Hospital, Bordeaux in Bordeaux,
France.^12

Soliris in aHUS Patients with Progressing TMA Despite Intensive PE/PI:
Three-year Update (Abstract SA-PO852)

In another poster presented today, researchers presented results from a
three-year update of a prospective, open-label, single-arm Phase 2 study in 17
adult and adolescent patients with aHUS who had presented with active,
progressing TMA. Seventeen patients were enrolled in the initial study and
received Soliris for 26 weeks. Thirteen of the 17 patients continued into a
long-term extension phase.^4

In patients with aHUS and clinical evidence of progressing TMA, investigators
reported that long-term Soliris treatment inhibited complement-mediated TMA,
as measured by rapid and sustained improvement in platelet count over three
years (mean change from baseline, P=0.0001 at 26 weeks and P<0.0001 at 3
years), as well as early achievement of hematologic normalization and TMA
event-free status (at least 12 consecutive weeks of stable platelet count, no
PE/PI, and no new dialysis). Additionally, long-term Soliris treatment was
associated with a rapid and sustained improvement in mean change of eGFR over
3 years (mean change from baseline, 32 ml/min/1.73m^2, P=0.001 at 26 weeks and
38 ml/min/1.73m^2, P<=0.0001 at the three-year update).^4

“The three-year safety and efficacy update data from this study highlight the
durability of Soliris and support the benefit of continued therapy in patients
with aHUS,” concluded A. Osama Gaber, Professor of Surgery at Weill Cornell
Medical College and Director of the Methodist J.C. Walter Transplant Center at
The Methodist Hospital in Houston, Texas.^13 “The data also support that
continued treatment with Soliris maintains beneficial long-term patient
outcomes in patients at risk from life-threatening complications of TMA.”

Initial Patient Characteristics from Global aHUS Registry (Abstract SA-PO853)

Also on November 9, Christoph Licht, M.D., FASN, Associate Professor of
Pediatrics, Division of Nephrology at The Hospital for Sick Children,
University of Toronto, presented baseline demographics from the initial
patients enrolled in the global aHUS Registry, which was established in April
2012 to prospectively collect information on patients with aHUS. As of
September 2013, a total of 211 patients had enrolled in the global aHUS
patient registry. The results and analyses collected within the Registry will
increase awareness and understanding of aHUS disease history and progression
in order to help optimize care and improve quality of life for patients with
aHUS.^5

About aHUS

aHUS is a chronic, ultra-rare, and life-threatening disease in which a genetic
deficiency in one or more complement regulatory genes causes chronic
uncontrolled complement activation, resulting in complement-mediated
thrombotic microangiopathy (TMA), the formation of blood clots in small blood
vessels throughout the body.^14,15 Permanent, uncontrolled complement
activation in aHUS causes a life-long risk for TMA, which leads to sudden,
catastrophic, and life-threatening damage to the kidney, brain, heart, and
other vital organs, and premature death.^14,16 Sixty-five percent of all
patients with aHUS die, require kidney dialysis, or have permanent kidney
damage within the first year after diagnosis despite plasma exchange or plasma
infusion (PE/PI).^8,17 The majority of patients with aHUS who receive a kidney
transplant commonly experience subsequent systemic TMA, resulting in a 90%
transplant failure rate in these TMA patients.^18

aHUS affects both children and adults. Complement-mediated TMA also causes
reduction in platelet count (thrombocytopenia) and red blood cell destruction
(hemolysis). While mutations have been identified in at least ten different
complement regulatory genes, mutations are not identified in 30-50% of
patients with a confirmed diagnosis of aHUS.^7

About Soliris

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 US (2007), European Union (2007), Japan (2010) 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. Soliris is also approved in the US (2011), European Union (2011),
and Japan (2013) as the first and only treatment for patients with atypical
hemolytic uremic syndrome (aHUS), a debilitating, ultra-rare and
life-threatening genetic disorder characterized by complement-mediated
thrombotic microangiopathy, or TMA (blood clots in small vessels). Soliris is
indicated to inhibit complement-mediated TMA. The effectiveness of Soliris in
aHUS is based on the effects on TMA and renal function. Prospective clinical
trials in additional patients, the preliminary results of which are reported
here at ASN, are ongoing to confirm the benefit of Soliris in patients with
aHUS. Soliris is not indicated for the treatment of patients with Shiga toxin
E. coli related hemolytic uremic syndrome (STEC-HUS). For the breakthrough
innovation in complement inhibition, Alexion and Soliris have 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
Rare Diseases. 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
infection.

About Alexion

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 nearly 50
countries for the treatment of PNH, and in the United States, European Union,
Japan and other countries for the treatment of aHUS. Alexion is evaluating
other potential indications for Soliris in additional severe and ultra-rare
disorders beyond PNH and aHUS, and is developing other highly innovative
biotechnology product candidates across multiple therapeutic areas. 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 anticipated clinical development, regulatory and commercial
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, 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, 2013, 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

     
       Greenbaum LA, Fila M, Tsimaratos M, et al. Eculizumab (ECU) inhibits
       thrombotic microangiopathy (TMA) and improves renal function in
(1)    pediatric atypical hemolytic uremic syndrome (aHUS) patients (pts).
       Presented at American Society of Nephrology (ASN) Kidney Week 2013,
       Atlanta, Ga., November 9, 2013. Abstract SA-PO849.
       
       Fakhouri F, Hourmant M, Campistol JM, et al. Eculizumab (ECU) inhibits
       thrombotic microangiopathy (TMA) and improves renal function in adult
(2)    patients (pts) with atypical hemolytic uremic syndrome (aHUS).
       Presented at American Society of Nephrology (ASN) Kidney Week 2013,
       Atlanta, Ga., November 8, 2013. Abstract FR-OR057.
       
       Delmas Y, Loirat C, Muus P, et al. Eculizumab (ECU) in atypical
       hemolytic uremic syndrome (aHUS) patients (pts) with long disease
(3)    duration and chronic kidney disease (CKD): sustained efficacy at 3
       years. Presented at American Society of Nephrology (ASN) Kidney Week
       2013, Atlanta, Ga., November 8, 2013. Abstract FR-PO536.
       
       Gaber O, Loirat C, Greenbaum L, et al. Eculizumab (ECU) maintains
       efficacy in atypical hemolytic uremic syndrome (aHUS) patients (pts)
(4)    with progressing thrombotic microangiopathy (TMA): 3-year (yr) update.
       Presented at American Society of Nephrology (ASN) Kidney Week 2013,
       Atlanta, Ga., November 9, 2013. Abstract SA-PO852.
       
       Licht C, Ardissino G, Ariceta G, et al. An observational,
       non-interventional, multicenter, multinational registry of patients
(5)    (pts) with atypical hemolytic uremic syndrome (aHUS): initial pt
       characteristics. Presented at American Society of Nephrology (ASN)
       Kidney Week 2013, Atlanta, Ga., November 9, 2013. Abstract SA-PO853.
       
(6)    Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med.
       2009;361:1676-87.
       
       Noris M, Caprioli J, Bresin E, et al. Relative role of genetic
(7)    complement abnormalities in sporadic and familial aHUS and their impact
       on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-59.
       
       Caprioli J, Noris M, Brioschi S, et al. The impact of MCP, CFH, and IF
(8)    mutations on clinical presentation, response to treatment, and outcome.
       Blood. 2006;108:1267-9.
       
       Vilalta R, Al-Akash S, Davin J, et al. Eculizumab therapy for pediatric
(9)    patients with atypical hemolytic uremic syndrome: efficacy and safety
       outcomes of a retrospective study [abstract 1155]. Haematologica.
       2012;97(suppl 1):479.
       
(10)   Dr. Larry Greenbaum receives research support from Alexion
       Pharmaceuticals, Inc. and is a consultant to the company.
       
(11)   Dr. Fadi Fakhouri receives research support from Alexion
       Pharmaceuticals, Inc. and is a consultant to the company.
       
(12)   Dr. Yahsou Delmas receives research support from Alexion
       Pharmaceuticals, Inc. and is a consultant to the company.
       
(13)   Dr. A. Osama Gaber receives research support from Alexion
       Pharmaceuticals, Inc. and is a consultant to the company.
       
(14)   Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin
       Nephrol Hypertens. 2010;19(3):242-7.
       
       Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation
(15)   and initial therapy of diarrhea-negative hemolytic uremic syndrome.
       Pediatr Nephrol. 2009;24:687-96.
       
(16)   Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney
       Int. 2006;70(1):16-23.
       
       Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T. Plasmatherapy in
(17)   atypical hemolytic uremic syndrome. Semin Thromb Hemost.
       2010;36:673-81.
       
       Bresin E, Daina E, Noris M, et al. Outcome of renal transplantation in
(18)   patients with non-Shiga toxin-associated hemolytic uremic syndrome:
       prognostic significance of genetic background. Clin J Am Soc Nephrol.
       2006;1:88-99.
       

Contact:

Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Executive Director, Corporate Communications
or
Media:
Alexion Pharmaceuticals, Inc.
Kim Diamond, 203-439-9600
Senior Director, Corporate Communications
or
Investors:
Rx Communications
Rhonda Chiger, 917-322-2569
 
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