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 in Adults and First Prospective
   Trial in Pediatrics with aHUS Confirm the Safety and Efficacy Profile of
                                  Soliris --

      –ASN Meeting Also Features Three-year Update Data from aHUS Study
         Highlighting Long-term Benefits of Chronic Soliris Therapy–

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. In two large, prospective,
multinational aHUS 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.^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 aHUS extension studies that highlighted the long-term
benefits of Soliris therapy. 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 approved for
the treatment of aHUS in the United States, European Union, Japan and other
countries.

“Results from four prospective studies in aHUS demonstrate a significant and
sustained inhibition of complement-mediated TMA with Soliris treatment,” 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, researchers presented positive results from the
first prospective trial of Soliris in pediatric patients with aHUS, which
follows the previously presented results of a retrospective study in pediatric
patients with aHUS .^9 This open-label, prospective, single-arm, mutlinational
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 adults 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.,
PhD., 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, European Union, 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 also approved in the US, the European Union, Japan and other
countries as the first and only treatment for patients with atypical Hemolytic
Uremic Syndrome (aHUS) to inhibit complement-mediated thrombotic
microangiopathy, a debilitating, ultra-rare and life-threatening genetic
disorder characterized by complement-mediated thrombotic microangiopathy
(blood clots in small vessels). The effectiveness of Soliris in aHUS is based
on the effects on thrombotic microangiopathy (TMA) and renal function. Soliris
is not indicated for the treatment of patients with Shiga toxin E. coli
related hemolytic uremic syndrome (STEC-HUS).

More information including the full prescribing information on Soliris is
available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000791/human_med_001055.jsp&mid=WC0b01ac058001d124

Important Safety Information

In Europe, the Summary of Product Characteristics (SmPC) for Soliris includes
a special warning and precaution for use: Due to its mechanism of action, the
use of Soliris increases the patient’s susceptibility to meningococcal
infection (Neisseria meningitidis). These patients might be at risk of disease
by uncommon serogroups (particularly Y, W135 and X), although meningococcal
disease due to any serogroup may occur. To reduce the risk of infection, all
patients must be vaccinated at least 2 weeks prior to receiving Soliris. aHUS
patients who are treated with Soliris less than 2 weeks after receiving a
meningococcal vaccine must receive treatment with appropriate prophylactic
antibiotics until 2 weeks after vaccination. Patients must be re-vaccinated
according to current medical guidelines for vaccination use. Tetravalent
vaccines against serotypes A, C, Y and W135 are strongly recommended,
preferably conjugated ones. Vaccination may not be sufficient to prevent
meningococcal infection. Consideration should be given to official guidance on
the appropriate use of antibacterial agents.

The most common or serious adverse reactions are headache (occurred mostly in
the initial phase), leukopenia and meningococcal infection. The most common
(>10%) adverse reactions reported in paediatric aHUS patients were diarrhoea,
vomiting, pyrexia, upper respiratory tract infection and headache. Soliris
treatment should not alter anticoagulant management. Please see Summary of
Product Characteristics for full prescribing information for Soliris,
including all special warnings and precautions.

About Alexion

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on the
development of treatments for severe and ultra-rare disorders through the
innovation, development and commercialisation of innovative therapeutic
products. Alexion is the global leader in complement inhibition.

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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