-- Soliris® Reduced the Risk of Adjudicated
On-Trial Relapse by 94.2% Compared to Placebo (p < 0.0001)
--
-- Safety Profile Consistent with that Seen in
Previous Studies and Real-World Use --
-- Preparing for Regulatory Submissions in the
US, European Union, and Japan --
-- Conference Call/Webcast Scheduled for Today,
Monday, September 24, 2018 at 8:30 a.m. EDT --
Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today announced
positive topline results from the Phase 3 PREVENT study of Soliris®
(eculizumab) in patients with anti-aquaporin-4 (AQP4) auto
antibody-positive neuromyelitis optica spectrum disorder (NMOSD).
NMOSD is a rare, devastating, complement-mediated disorder of the
central nervous system characterized by relapses. Each relapse
results in stepwise accumulation of disability, including blindness
and paralysis, and sometimes premature death.1,2,3 Patients who
have anti-AQP4 auto-antibodies represent approximately three
quarters of all patients with NMOSD.4,5,6,7 There are currently no
approved therapies for this disease.
The study met its primary endpoint of time to first adjudicated
on-trial relapse, demonstrating that treatment with Soliris®
reduced the risk of NMOSD relapse by 94.2 percent compared to
placebo (p < 0.0001). At 48 weeks, 97.9 percent of patients
receiving Soliris® were free of relapse compared to 63.2 percent of
patients receiving placebo. Soliris® was generally well tolerated
with a safety profile consistent with that seen in previous
clinical studies and real-world use in its three approved
indications. No cases of meningococcal infection were observed.
“These results far exceeded our expectations. The remarkable
reduction in relapse risk demonstrates the unique ability of
Soliris® to inhibit complement, and suggests a promising new
treatment for NMOSD,” said John Orloff, M.D., Executive Vice
President and Head of Research & Development at Alexion. “Given
that patients currently have no approved therapies, we are moving
quickly to discuss these results with regulators and file for
approval in the U.S., EU, and Japan.”
“The primary goal in treating NMOSD is relapse prevention as
each relapse further increases disability, which makes this disease
so devastating. For decades, we have been hoping for a therapy that
can prevent relapse and subsequent accumulation of disability by
addressing a critical underlying cause of the disease,” said
Michael Levy, M.D., Ph.D., Associate Professor at Johns Hopkins
University, and Director of the Neuromyelitis Optica Clinic in
Baltimore, MD. “The substantial effect of Soliris® seen in this
groundbreaking randomized, controlled study in NMOSD could
potentially become a turning point for patients and their families
who live in constant fear of relapse.”
Detailed results from this Phase 3 study will be presented at a
future medical congress.
About NMOSDNMOSD is a rare, devastating,
complement-mediated disorder of the central nervous system (CNS).
Patients experience an unpredictable, relapsing, and deteriorating
course of disease with each relapse adding to the disability, and
potentially leading to premature death. Optic neuritis can cause
eye pain and blindness. Transverse myelitis can cause severe
weakness, impaired mobility, sensory and motor disability, loss of
bowel and bladder function, paralysis, and respiratory
failure.3,8,9 Significant proportions of patients sustain permanent
severe disability, including blindness and paralysis, or die within
six years (75 months) of disease onset. Specifically, one third (34
percent) of patients sustain permanent motor disability, almost one
quarter (23 percent) become wheelchair-dependent, almost one fifth
(18 percent) suffer from permanent visual disability, and almost
one in 10 (9 percent) die.10
Patients with anti-aquaporin-4 (AQP4) auto-antibodies represent
approximately three quarters of all patients with NMOSD.4,5,6,7 The
disease primarily affects women.11 There are currently no approved
therapies for this disease.
In patients with NMOSD, the body’s own immune system can turn on
itself to produce auto-antibodies (immunoglobulin G [IgG)]) against
AQP4, a protein on certain cells in the brain and spinal cord that
are critical for the survival of nerve cells. The binding of these
anti-AQP4 auto-antibodies activates the complement cascade, another
part of the immune system. Complement activation by anti-AQP4
auto-antibodies leads to destruction of vital cells in the CNS,
leading to demyelination and to the death of neurons, predominantly
in the spinal cord and optic nerve, which ultimately results in
blindness, paralysis, and sometimes death.12,13,14,15,16
About the PREVENT StudyThe Prevention of Relapses and
Evaluation of Eculizumab in NMOSD Treatment (PREVENT) study was a
multinational, double-blind, parallel-group Phase 3 time-to-event
study that assessed the efficacy and safety of Soliris®
(eculizumab) compared to placebo for the treatment of patients with
anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica
spectrum disorder (NMOSD). The study enrolled 143 adult patients
who were randomized 2:1 to the Soliris® and placebo treatment arms.
Patients needed to have a confirmed diagnosis of NMOSD, be
seropositive for anti-AQP4 auto-antibodies (also called
NMO-immunoglobulin G [IgG] antibodies), and have a history of at
least two relapses in the last 12 months or three relapses in the
last 24 months, with at least one relapse in the 12 months prior to
screening. Patients were allowed to receive stable maintenance dose
of protocol permitted supportive immune suppressive therapies for
relapse prevention.
The primary endpoint was the time to first on-trial relapse as
adjudicated by an independent committee comprised of three external
experts in neurology/neuro-ophthalmology who were blinded to
treatment. Adjudication decisions were based on objective and
consistent clinical criteria described in a relapse adjudication
charter. Secondary endpoints included adjudicated on-trial
annualized relapse rate, and others assessing disability and
quality of life, as well as safety and tolerability measures.
Pre-specified sensitivity analyses include various types of
statistical analyses of the time to relapse, and of secondary
endpoints.
The study met its primary endpoint of time to first adjudicated
on-trial relapse, demonstrating that treatment with Soliris®
reduced the risk of NMOSD relapse by 94.2 percent compared to
placebo (p < 0.0001). At 48 weeks, 97.9 percent of patients
receiving Soliris® were free of relapse compared to 63.2 percent of
patients receiving placebo. Treatment with Soliris® reduced the
adjudicated on-trial annualized relapse rate compared to placebo, a
key secondary endpoint, by 95.5 percent (p<0.0001).
While results favored Soliris® on the other secondary endpoints,
which included disability and quality of life measures, the
observed differences were small. This was not unexpected since
disease worsening in NMOSD is driven by damage incurred following
relapse. Follow-up for assessment of long-term disability was
limited by the trial design, which permitted patients to transition
to the open-label study six weeks after the relapse, where all
patients received Soliris®. Soliris® was generally well tolerated
with a safety profile consistent with that seen in previous
clinical studies and real-world use in its three approved
indications. No cases of meningococcal infection were observed.
The treatment duration for an individual patient varied as this
was a time-to-event study. Patients who completed the study either
because of a relapse or because the study ended were provided with
the opportunity to enter an extension study to receive open-label
Soliris®. One hundred and nineteen patients entered the extension
study.
Conference CallAlexion will host a conference
call/webcast today, Monday, September 24, 2018 at 8:30 a.m. EDT to
discuss the study data. To participate in this call, dial (866)
762-3111 (USA) or +1 (210) 874-7712 (International), passcode
1296796, shortly before 8:30 a.m. EDT. A replay of the call will be
available for a limited period of time following the call. The
audio webcast can be accessed on the Investors page of Alexion’s
website at: http://ir.alexion.com.
About Soliris® (eculizumab)Soliris® is a
first-in-class complement inhibitor that works by inhibiting the C5
protein in the terminal part of the complement cascade, a part of
the immune system that, when activated in an uncontrolled manner,
plays a role in severe rare and ultra-rare disorders like
paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic
uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR)
antibody-positive myasthenia gravis (MG). Soliris® is approved in
the U.S., EU, Japan, and other countries as the first and only
treatment for patients with PNH and aHUS, in the EU as the first
and only treatment of refractory generalized MG (gMG) in adults who
are anti-AchR antibody-positive, in the U.S. for the treatment of
adult patients with gMG who are anti-AchR antibody-positive, and in
Japan for the treatment of patients with gMG who are AChR
antibody-positive and whose symptoms are difficult to control with
high-dose intravenous immunoglobulin (IVIG) therapy or
plasmapheresis (PLEX). Soliris® is not indicated for the treatment
of patients with Shiga-toxin E. coli-related hemolytic uremic
syndrome (STEC-HUS).
Soliris® has received Orphan Drug Designation (ODD) for the
treatment of patients with PNH in the U.S., EU, Japan, and many
other countries, for the treatment of patients with aHUS in the
U.S., EU, and many other countries, for the treatment of patients
with MG in the U.S. and EU, for the treatment of patients with
refractory gMG in Japan, and for the treatment of patients with
NMOSD in the U.S., EU, and Japan. Alexion and Soliris® have
received some of the pharmaceutical industry's highest honors for
the medical innovation in complement inhibition: the Prix Galien
USA (2008, Best Biotechnology Product) and France (2009, Rare
Disease Treatment).
For more information on Soliris®, please see full prescribing
information for Soliris®, including BOXED WARNING regarding risk of
serious meningococcal infection, available at www.soliris.net.
Important Soliris® Safety InformationThe
U.S. prescribing information for Soliris® includes the following
warnings and precautions: 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 Centers for Disease Control (CDC)’s Advisory Committee on
Immunization Practices (ACIP) recommendations for meningococcal
vaccination in patients with complement deficiencies. Immunize
patients with meningococcal vaccines at least two weeks prior to
administering the first dose of Soliris®, unless the risks of
delaying Soliris® therapy outweigh the risk of developing a
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) or
at www.solirisrems.com.
Patients may have increased susceptibility to infections,
especially with encapsulated bacteria. Aspergillus infections have
occurred in immunocompromised and neutropenic patients. Children
treated with Soliris® may be at increased risk of developing
serious infections due to Streptococcus pneumoniae and Haemophilus
influenza type b (Hib). 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. Administration of Soliris® may result in
infusion reactions, including anaphylaxis or other hypersensitivity
reactions.
In patients with PNH, the most frequently reported adverse
events observed with Soliris® treatment in clinical studies were
headache, nasopharyngitis, back pain, and nausea. In patients with
aHUS, the most frequently reported adverse events observed with
Soliris® treatment in clinical studies were headache, diarrhea,
hypertension, upper respiratory infection, abdominal pain,
vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea,
urinary tract infections, and pyrexia. In patients with gMG who are
anti-AchR antibody-positive, the most frequently reported adverse
reaction observed with Soliris® treatment in the placebo-controlled
clinical study (≥10%) was musculoskeletal pain.
About AlexionAlexion is a global biopharmaceutical
company focused on serving patients and families affected by rare
diseases through the discovery, development, and commercialization
of life-changing therapies. As the global leader in complement
biology and inhibition for more than 20 years, Alexion has
developed and commercializes the first and only approved complement
inhibitor to treat patients with paroxysmal nocturnal
hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS),
and anti-acetylcholine receptor (AchR) antibody-positive
generalized myasthenia gravis (gMG). Alexion also has two highly
innovative enzyme replacement therapies for patients with
life-threatening and ultra-rare metabolic disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency
(LAL-D). In addition, the company is developing two late-stage
therapies, a second complement inhibitor and a copper-binding agent
for Wilson disease. Alexion focuses its research efforts on novel
molecules and targets in the complement cascade, and its
development efforts on the core therapeutic areas of hematology,
nephrology, neurology, and metabolic disorders. Alexion has been
named to the Forbes list of the World's Most Innovative Companies
seven years in a row and is headquartered in Boston, Massachusetts'
Innovation District. The company also has offices around the globe
and serves patients in more than 50 countries. This press release
and further information about Alexion can be found at:
www.alexion.com.
[ALXN-G]
Forward-Looking StatementThis press release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements
related to: the impact that the relapse reduction could have for
patients with NMOSD using Soliris®, complement inhibition can play
a critical role in treating NMOSD, Soliris® may be a promising new
treatment for NMOSD and a turning point in the treatment of this
condition for patients and their families, the future planned
submission of regulatory applications for review and approval by
regulatory authorities in the U.S., the European Union and Japan
for Soliris® as a treatment for NMOSD, future plans to present
additional results and findings from Phase 3 of the PREVENT Study,
and the potential medical benefits of Soliris® for the treatment of
NMOSD and other diseases. Forward-looking statements are subject to
factors that may cause Alexion's results and plans to differ
materially from those expected by these forward looking statements,
including for example: the inability to submit regulatory
applications for Soliris® as a treatment for NMOSD for review and
approval by certain governmental authorities (or an unexpected
delay in the timeframes for such submissions) due to increased
expense, manufacturing delays or other reasons, the possibility
that results of clinical trials are not predictive of safety and
efficacy results of our products in broader patient populations
(including Soliris® as a treatment for NMOSD), the inability to
timely provide (or provide at all) the product safety and efficacy
information required by regulatory authorities for Soliris® as a
treatment for NMOSD, our products not gaining acceptance among
patients (and providers or third party payers) for certain
indications (due to cost or otherwise), the inability to develop
future clinical study programs for certain product delivery
mechanisms (or the failure of those programs to meet safety and
efficacy goals), unforeseen safety issues resulting from the
administration of products and product candidates in patients,
including serious complications or side effects, the inability to
timely and cost-effectively develop programs for existing products
for new indications (or the failure to obtain regulatory approval
for use in such new indications), the introduction of competing
drugs and product candidates for NMOSD, decisions of regulatory
authorities regarding the adequacy of our research, marketing
approval or material limitations on the marketing of our products
(or the indications of such products), delays, interruptions, or
failures in the manufacture and supply of our products and our
product candidates, failure to satisfactorily address matters
raised by the FDA and other regulatory agencies, the possibility
that current rates of adoption of our products are not sustained
(or do not meet expected future rates), the possibility that
clinical trials of our product candidates could be delayed, the
adequacy of our pharmacovigilance and drug safety reporting
processes, the risk that third party payers (including governmental
agencies) will not reimburse or continue to reimburse for the use
of our products (or proposed future products) at acceptable rates
or at all, uncertainties surrounding legal proceedings, company
investigations and government investigations, including
investigations of Alexion by the U.S. Securities and Exchange
Commission (SEC) and U.S. Department of Justice, the risk that
other anticipated regulatory filings are delayed, the risk that
estimates regarding the number of patients with the diseases that
our products treat are inaccurate, and a variety of other risks set
forth from time to time in Alexion's filings with the SEC,
including but not limited to the risks discussed in Alexion's
Quarterly Report on Form 10-Q for the period ended June 30, 2018
and in Alexion's other filings with the SEC. Alexion disclaims any
obligation 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 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ,
Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neuro.
2007;6(9):805-15.2 Wingerchuk DM. Diagnosis and treatment of
neuromyelitis optica. Neurologist. 2007;13(1):2-11.3 Wingerchuk DM,
Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol.
2008;10(1):55-66.4 Cossburn M et al. The prevalence of
neuromyelitis optica in South East Wales. European Journal of
Neurology. 2012;19: 655-659.5 Flanagan EP et al. Epidemiology of
Aquaporin-4 Autoimmunity and Neuromyelitis Optica Spectrum.
AnnNeurol. 2016;79:775–783.6 Cabrera-Gomez JA et al. An
epidemiological study of neuromyelitis optica in Cuba. J Neurol.
2009 256:35–447 Miyamoto K ety al. Nationwide epidemiological study
of neuromyelitis optica in Japan. J Neurol Neurosurg Psychiatry
Month. 2018 Vol 0 No 0.8 Tuzun E, Kurtuncu M, Turkoglu R, et al.
Enhanced complement consumption in neuromyelitis optica and
Behcet’s disease patients. J Neuroimmunol. 2011;233(1-2):211-5.9
Kuroda H, Fujihara K, Takano R, et al. Increase of complement
fragment C5a in cerebrospinal fluid during exacerbation of
neuromyelitis optica. J Neuroimmunol. 2013;254(1-2):178-82.10
Kitley J. et al. Prognostic factors and disease course in
aquaporin-4 antibody-positive patients with neuromyelitis optica
spectrum disorder from the United Kingdom and Japan. Brain. 2012;
135: 1834-1849.11 Wingerchuk DM. Neuromyelitis optica. Int MS J.
2006;13(2):42–50.12 Jarius S, Wildemann B. AQP4 antibodies in
neuromyelitis optica: diagnostic and pathogenetic relevance. Nat
Rev Neuro. 2010;6:383-92.13 Hinson SR, Romero MF, Popescu BFG, et
al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to
aquaporin-4 in astrocytes. Proc Nat Acad Sci.
2012;109(4):1245-50.14 Hinson SR, Pittock SJ, Lucchinetti CF, et
al. Pathogenic potential of IgG binding to water channel
extracellular domain in neuromyelitis optica. Neurology.
2007;69:2221-31.15 Verkman, A.S. Aquaporins in clinical medicine.
Annu Rev Med. 2012;63:303-316.16 Papadopoulos, M.C. et al.
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Alexion Pharmaceuticals, Inc.MediaArne Naeveke, PhD,
857-338-8597orInvestorsSusan Altschuller, PhD, 857-338-8788
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