Soliris® Significantly Improved Clinical Outcomes in Patients with aHUS in Pivotal Trials Published in New England Journal of

  Soliris® Significantly Improved Clinical Outcomes in Patients with aHUS in
  Pivotal Trials Published in New England Journal of Medicine

— Findings Underscore Importance of Earlier Intervention and Chronic Terminal
          Complement Inhibition with Soliris in Patients with aHUS—

   —Improved Clinical Outcomes Include Recovery of Severely Impaired Kidney

Business Wire

CHESHIRE, Conn. -- June 5, 2013

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that data
published in the June 6 issue of The New England Journal of Medicine (NEJM)
demonstrate that  chronic Soliris^® (eculizumab) therapy is effective in the
treatment of patients with atypical hemolytic uremic syndrome (aHUS), a
genetic, life-long, ultra-rare disease associated with vital organ failure and
premature death.^1 In patients with aHUS, uncontrolled terminal complement
activation causes thrombotic microangiopathy (TMA), the formation of blood
clots in small blood vessels throughout the body.^2,3

According to results of two pivotal studies published in the NEJM, chronic
Soliris treatment substantially inhibits systemic complement-mediated TMA,
decreases the need for TMA-related intervention, results in significant and
sustained improvement in platelet count, increasingly improves renal function
across patient groups over time, and is associated with substantial kidney
recovery in patients with aHUS. In addition, chronic Soliris treatment leads
to reversal of vital organ damage and significant improvements in
health-related quality of life (HRQoL). ^ The study data also indicate that
earlier intervention with Soliris improves clinical outcomes.^1

aHUS is a chronic and life-threatening condition that can progressively damage
vital organs, leading to stroke, heart attack, kidney failure, and death.^4
The morbidities and premature mortality in aHUS are caused by chronic,
uncontrolled activation of the terminal complement system, resulting in
systemic TMA.^5,6 Soliris, a first-in-class terminal complement inhibitor, is
indicated for the treatment of patients with aHUS to inhibit
complement-mediated TMA.

“Soliris represents a substantial advance in the treatment of patients who
suffer from aHUS, because it directly targets chronic, uncontrolled complement
activation, the underlying cause of the progressive organ failure and
shortened life span of patients with aHUS,” said lead study author Christophe
Legendre, M.D., Professor of Nephrology at the University of Paris Descartes
and Hôpital Necker in Paris, France. “With an approved and highly effective
treatment supported by strong peer-reviewed data, physicians must be vigilant
in differentially diagnosing patients with aHUS, rapidly initiating treatment,
and complying with approved dosing regimens to prevent the lifelong risk of
systemic clinical complications of TMA, including damage to multiple vital
organ systems.”

Soliris was approved for the treatment of patients with aHUS in the United
States, Europe and other countries based on data from the two prospective
studies published today in NEJM, together with data from a separate
retrospective study.^7 Soliris is the first and only approved treatment for
aHUS, and directly addresses the underlying cause of the disease – chronic,
uncontrolled terminal complement activation leading to systemic
complement-mediated TMA. Prior to the availability of Soliris, up to 65
percent of patients sustained permanent renal damage, progressed to end-stage
renal disease (ESRD), or died within a year of aHUS diagnosis.^8

"We are working with a sense of urgency to bring Soliris to more patients
suffering from this life-threatening disease worldwide,” said study co-author
Camille Bedrosian, M.D., senior vice president and chief medical officer of
Alexion Pharmaceuticals, Inc. “In these clinical trials, earlier intervention
with Soliris, in order to achieve the complete and chronic inhibition of
terminal complement activity, substantially improved the health of a broad
population of patients with aHUS.”

Clinical Trial Data Published in NEJM

The data published in the NEJM are based on two prospective, multicenter Phase
2 trials (referred to as Trial 1 and Trial 2) in which aHUS patients aged 12
years or older received Soliris for 26 weeks as well as during long-term
extensions of each trial (median durations of 64 and 62 weeks for the combined
trial and extensions of Trials 1 and 2, respectively). ^ Trial 1 enrolled 17
patients with low platelet counts and substantial kidney damage with clinical
evidence of progressing TMA, and a median time from aHUS diagnosis to
screening of 9.7 months. Trial 2 enrolled 20 patients with chronic renal
insufficiency, prolonged use of plasma exchange or infusion, and long-term
aHUS, with a median time from aHUS diagnosis to screening of 48 months.^1

In both trials, Soliris significantly reduced complement-mediated TMA, as
indicated by normalization of hematologic measures and reduction in TMA
intervention. In Trial 1, the increase in platelet count from baseline to week
26 was 73x10^9 per liter (P<0.001). In Trial 2, 80 percent of the patients
achieved TMA event-free status. Soliris significantly reduced terminal
complement activity within one hour after treatment initiation in both trials,
and all Soliris-treated patients achieved complete terminal complement
activity inhibition, which they maintained with ongoing treatment (P<0.001 for
both trials through week 26).^1

Both trials also demonstrated positive results in secondary endpoints. Soliris
therapy significantly improved renal outcomes and was associated with
continuous, time-dependent increases in estimated glomerular filtration rate
(eGFR), a measure of kidney function. In Trial 1, dialysis was discontinued in
four of five patients (80 percent) who had required dialysis at the time of
initiating Soliris therapy; these patients remained dialysis-free throughout
the course of treatment. In addition, 65 and 45 percent of Trial 1 and Trial 2
patients, respectively, experienced an improvement in kidney function by at
least one chronic kidney disease (CKD) stage during the study extension

In both trials, investigators noted that earlier Soliris initiation was
associated with significantly greater improvements in kidney function (P=0.007
in Trial 1 and P<0.001 in Trial 2), ^ suggesting that starting Soliris
treatment earlier may lead to improved clinical outcomes and reversal of organ

In Trials 1 and 2, 24 and 35 percent, respectively, of patients had no
identified complement regulatory factor gene mutation or autoantibody (i.e.,
to complement factor H [CFH]). Of note, in both trials, similarly positive
outcomes were achieved in patients treated with Soliris regardless of the
presence or absence of identified genetic mutations or CFH autoantibodies.^5
This finding lends support to the study authors’ recommendation that treatment
with Soliris in aHUS patients be considered without requiring the results of
complement mutation testing.^1

Deviation from approved Soliris dosing exposes aHUS patients to the ongoing
lifelong risk of systemic clinical complications of TMA, including multiple
vital organ damage, the study authors reported.^1,9,10,11 Five of 18 patients
who missed Soliris doses in the two trials or the retrospective study
experienced severe subsequent TMA complications.^1,12,13 These findings are
consistent with the pathophysiology of the disease (uncontrolled complement
activation) and underscore the importance of continued patient monitoring and
sustained Soliris treatment to reduce TMA.^1,13,14

Soliris appeared to be well tolerated in the two studies. The most common
serious adverse events (SAEs) with Soliris treatment were accelerated
hypertension, hypertension and influenza. There was no apparent increase in
SAEs with ongoing Soliris treatment, as rates of SAEs remained steady or
declined from the initial 26-week study period to the subsequent treatment
periods. No new SAEs emerged after the initial 26-week study period. SAEs were
similar among patient subgroups, including 15 transplant patients who received
immunosuppressive therapy during the trials. All patients were alive at the
time of the data cut-off in the trial.^1 The trials are registered at NCT00844844, NCT00844545, NCT00844428, NCT00838513.

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 United States, 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
Rare Diseases.

More information, including the full prescribing information on Soliris, is
available at

Important Safety Information

Soliris is generally well tolerated in patients with PNH and aHUS. In patients
with PNH, the most frequently reported adverse events observed with Soliris
treatment in clinical studies were headache, nasopharyngitis (runny nose), and
back pain. 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, and diarrhea.

The US product label for Soliris also 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 (5.2). Enrollment in the Soliris REMS program and
additional information are available by telephone: 1-888-soliris

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 a treatment for patients with PNH and aHUS, two debilitating,
ultra-rare and life-threatening disorders caused by chronic uncontrolled
complement activation. The treatment is currently approved in more than 40
countries for the treatment of PNH, and in the United States and the European
Union for the treatment of aHUS. Alexion is evaluating other potential
indications for its marketed drug and is developing four other highly
innovative biotechnology product candidates, which are being investigated
across nine severe and ultra-rare disorders beyond PNH and aHUS. This press
release and further information about Alexion Pharmaceuticals, Inc. can be
found at:


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 PNH and 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
March 31, 2013. 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 Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor
eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med

^2 Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin
Nephrol Hypertens 2010 May;19(3):242-7

^3 Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int
2006 Jul;70(1):16-23.

^4 Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med.

^5 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.

^6 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.

^7 Eculizumab (Soliris). Silver Spring, MD: U.S. Food and Drug Administration
(FDA), Center for Drug Evaluation and Research (CDER); Sept 23, 2011.
Available at:

^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.

^9 Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémaux-Bacchi V,
Legendre C. New insights into postrenal transplant hemolytic uremc syndrome.
Nat Rev Nephrol 2011;7:23-35.

^10 Larrea CF, Cofan F, Oppenheimer F, Campistol JM, Escolar G, Lozano M.
Efficacy of eculizumab in the treatment of recurrent atypical hemolytic-uremic
syndrome after renal transplantation. Transplantation 2010;89:903-4.

^11 Mache CJ, Acham-Roschitz B, Frémaux-Bacchi V, et al. Complement inhibitor
eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol

^12 Electronic Medicines Compendium. Soliris: summary of product
characteristics. Available at:

^13 Soliris^® (eculizumab) U.S. prescribing information. Cheshire, CT: Alexion
Pharmaceuticals, Inc.; 2012. Available at:

^14 Zuber J, Fakouri F, Roumenina LT, Loirat C, Frémaux-Bacchi V. Use of
eculizumab for atypical hemolytic uraemic syndrome and C3 glomerulopathies.
Nat Rev Nephrol 2012;8:643-57.


Alexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Executive Director, Corporate Communications
Rx Communications
Rhonda Chiger, 917-322-2569
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