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- 
CHESHIRE, CT, Nov. 9, 2013 /CNW/ - 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.(3,4)Additionally, 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 systemic TMA.(7,8)Soliris, 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 
Paediatrics, 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. 
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 
(1)       Greenbaum LA, Fila M, Tsimaratos M, et al. Eculizumab (ECU) 


          inhibits thrombotic microangiopathy (TMA) and improves renal
          function in 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.
           

(2)       Fakhouri F, Hourmant M, Campistol JM, et al. Eculizumab (ECU)
          inhibits thrombotic microangiopathy (TMA) and improves renal
          function in adult 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.
           

(3)       Delmas Y, Loirat C, Muus P, et al. Eculizumab (ECU) in
          atypical hemolytic uremic syndrome (aHUS) patients (pts) with
          long disease 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.
           

(4)       Gaber O, Loirat C, Greenbaum L, et al. Eculizumab (ECU)
          maintains efficacy in atypical hemolytic uremic syndrome
          (aHUS) patients (pts) 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.
           

(5)       Licht C, Ardissino G, Ariceta G, et al. An observational,
          non-interventional, multicenter, multinational registry of
          patients (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.
           

(7)       Noris M, Caprioli J, Bresin E, et al. Relative role of
          genetic complement abnormalities in sporadic and familial
          aHUS and their impact on clinical phenotype. Clin J Am Soc
          Nephrol. 2010;5:1844-59.
           

(8)       Caprioli J, Noris M, Brioschi S, et al. The impact of MCP,
          CFH, and IF mutations on clinical presentation, response to
          treatment, and outcome. Blood. 2006;108:1267-9.
           

(9)       Vilalta R, Al-Akash S, Davin J, et al. Eculizumab therapy for
          pediatric 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.
           

(15)      Ariceta G, Besbas N, Johnson S, et al. Guideline for the
          investigation 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.
           

(17)      Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T.
          Plasmatherapy in atypical hemolytic uremic syndrome. Semin
          Thromb Hemost. 2010;36:673-81.
           

(18)      Bresin E, Daina E, Noris M, et al. Outcome of renal
          transplantation in patients with non-Shiga toxin-associated
          hemolytic uremic syndrome: prognostic significance of genetic
          background. Clin J Am Soc Nephrol. 2006;1:88-99.









SOURCE  Alexion Pharmaceuticals, Inc. 
Contacts 
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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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