- New data published in NEJM confirm sustained
three-year treatment effect -
- Data will also be presented in Emerging
Science session at American Academy of Neurology Annual Meeting
-
- SOLIRIS for NMOSD currently under regulatory
review in the U.S., European Union and Japan; U.S. FDA Priority
Review action date of June 28, 2019 -
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that
the New England Journal of Medicine (NEJM) published positive data
from the Phase 3 PREVENT study of SOLIRIS® (eculizumab), a
first-in-class complement inhibitor, in adult patients with
anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica
spectrum disorder (NMOSD). NMOSD is a rare and devastating,
autoimmune, inflammatory disorder of the central nervous system
(CNS) characterized by sudden and unpredictable relapses, also
known as attacks. Each relapse results in stepwise accumulation of
disability, including blindness and paralysis and sometimes
premature death. Uncontrolled complement activation triggered by
anti-AQP4 auto antibodies is a major underlying mechanism of the
disease.1,2,3 There is currently no approved therapy for patients
with NMOSD. Today’s NEJM online publication coincides with the
American Academy of Neurology (AAN) Annual Meeting, May 4-10, 2019
in Philadelphia, where these data will also be presented in the
Emerging Science session on May 7.
As announced previously, 97.9 percent of patients receiving
SOLIRIS were relapse-free at 48 weeks compared with 63.2 percent of
patients receiving placebo. New data published in NEJM and to be
presented for the first time at the AAN meeting confirm that the
significant relapse reduction observed in the PREVENT study was
sustained through three years of treatment. All patients receiving
SOLIRIS monotherapy and the vast majority of patients receiving
SOLIRIS in addition to immunosuppressive therapy (IST) were
relapse-free. The safety profile of SOLIRIS was consistent with
that seen in other clinical studies.
“Patients with NMOSD live in constant fear of an attack or
relapse. In this devastating disease, where each relapse results in
further disability, preventing relapses is the primary goal of
treatment,” said Sean Pittock, M.D., principal investigator of the
PREVENT study, lead author of the NEJM article and director of Mayo
Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology and
Mayo’s Neuroimmunology Laboratory in Rochester, Minnesota. “The
results from the PREVENT study, the first placebo-controlled Phase
3 study in NMOSD, are groundbreaking and demonstrate that the vast
majority of patients receiving eculizumab did not experience a
relapse.”
“The substantial reduction in relapse risk sustained through
three years of SOLIRIS treatment was consistent across all
patients, regardless of their baseline immunosuppressive therapy
use,” said John Orloff, M.D., Executive Vice President and Head of
Research & Development at Alexion. “These results provide hope
for a promising new way of treating patients with NMOSD, who
currently have no approved treatment options.”
Proportion of relapse-free patients
over time* in the PREVENT study, based on the primary
endpoint of time to first adjudicated on-trial relapse, as
published in NEJM and presented at AAN
Patients treated
(n at baseline [0 weeks])
Proportion of relapse-free patients [%] 48
weeks
(n)
96 weeks
(n)
144 weeks
(n)
All patients (100%)† SOLIRIS 97.9 96.4 96.4
(96) (68) (46) (22) Placebo
(47)
63.2
(21)
51.9
(9)
45.4
(4)
Patients receiving concomitant supportive IST (76.2%)‡
SOLIRIS
(75)
97.3
(54)
95.4
(35)
95.4
(13)
Placebo
(34)
64.3
(17)
55.0
(7)
55.0
(3)
Patients not receiving concomitant supportive IST (23.8%)‡
SOLIRIS
(21)
100.0
(14)
100.0
(11)
100.0
(9)
Placebo
(13)
60.6
(4)
40.4
(2)
20.2
(1)
p-values from log-rank tests are all <0.0001. IST:
Immunosuppressive therapy * Based on the Kaplan-Meier product limit
method. † Primary endpoint ‡ Summaries for subgroups with different
concomitant supportive IST were pre-specified. Statistical testing
was post-hoc. In this summary, the individual concomitant
supportive IST subgroups were combined.
The most common adverse events observed in the PREVENT study
were upper respiratory tract infection (29% of patients in the
SOLIRIS group vs. 13% in the placebo group), headache (23 vs. 23%),
nasopharyngitis (21 vs. 19%), and nausea (17 vs. 26%). The serious
adverse events that were reported for more than one patient in
either group were pneumonia (three patients in the SOLIRIS group
vs. one patient in the placebo group) and cellulitis, sepsis and
urinary tract infection (two patients for each event in the SOLIRIS
group vs. no patient in the placebo group). One patient receiving
SOLIRIS and concomitant supportive IST died from infectious pleural
effusion. The patient had an extensive history of pulmonary disease
and was an active smoker. No cases of meningococcal infection were
observed in the study.
The U.S. Food and Drug Administration (FDA), the European
Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical
Devices Agency (PMDA) are reviewing Alexion’s applications for
approval of SOLIRIS as a treatment for patients with NMOSD who are
anti-AQP4 antibody-positive. The FDA granted priority review and
set a Prescription Drug User Fee Act (PDUFA) action date of June
28, 2019.
About the PREVENT StudyThe Prevention of Relapses and
Evaluation of Eculizumab in NMOSD Treatment (PREVENT) study was a
multinational (70 sites in 18 countries), 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 were required 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 NMOSD relapses. Patients were
allowed to receive stable maintenance doses of protocol permitted
supportive immune suppressive therapies (ISTs) for relapse
prevention. Almost 25 percent of patients did not receive ISTs
during the study. Patients were vaccinated against Neisseria
meningitidis before receiving study treatment.
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 assignment. Adjudication decisions were based on
objective and consistent clinical criteria described in a relapse
adjudication charter. 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
open-label extension study to receive SOLIRIS. One hundred and
nineteen patients entered the extension study.
About NMOSDNeuromyelitis optica spectrum disorder (NMOSD)
is a rare and devastating, autoimmune, inflammatory disorder of the
central nervous system (CNS), typically involving the optic nerves
and spinal cord. Patients experience an unpredictable, relapsing,
and deteriorating course of disease with each attack, or relapse
adding to their disability, and potentially leading to premature
death.1,2,3,4 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.3,5,6 One third (34%) of
patients sustain permanent motor disability, almost one quarter
(23%) become wheelchair-dependent, almost one fifth (18%) suffer
from permanent visual disability, and almost one in 10 (9%) die.7
The disease primarily affects women.8 There is currently no
approved therapy for patients with NMOSD.
In patients with NMOSD, uncontrolled complement activation
triggered by auto-antibodies against anti-aquaporin-4 (AQP4), a
water channel protein present on certain cells (astrocytes) in the
CNS, results in the destruction of these cells, an increased
permeability of the blood brain barrier, the destruction of cells
(oligodendrocytes) surrounding nerve cells, the damage of the
covering of nerve cells (demyelination) and ultimately the death of
these nerve cells, predominantly in the optic nerves and spinal
cord. This damage causes the relapses, which can ultimately result
in blindness, paralysis and sometimes death.9,10,11,12,13 Patients
with AQP4 auto antibodies represent approximately three quarters of
all patients with NMOSD.14,15,16,17
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. The terminal complement cascade, 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),
anti-acetylcholine receptor (AchR) antibody-positive myasthenia
gravis (MG), and anti-aquaporin-4 (AQP4) antibody-positive
neuromyelitis optica spectrum disorder (NMOSD). SOLIRIS is approved
in the U.S., EU, Japan and other countries as a treatment for adult
patients with PNH and for adults and children with aHUS. SOLIRIS is
not indicated for the treatment of patients with Shiga-toxin E.
coli-related hemolytic uremic syndrome (STEC-HUS). In the U.S.,
SOLIRIS is also approved for the treatment of adult patients with
generalized MG (gMG) who are anti-AchR antibody-positive, in the EU
as the first and only approved treatment of refractory gMG in
adults 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 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 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).
Dr. Pittock reports grants, personal fees and nonfinancial
support from Alexion; grants from Grifols S.A. and Autoimmune
Encephalitis Alliance; and grants, personal fees, nonfinancial and
other support from Viela Bio. Dr. Pittock has patent No. 9,891,219
(application No. 12-573942), "Methods for Treating Neuromyelitis
Optica by Administration of Eculizumab to an Individual That Is
Aquaporin-4 (AQP4)-IgG Autoantibody Positive."
U.S. Indication for SOLIRIS®
(eculizumab)SOLIRIS is a prescription medicine called a
monoclonal antibody. SOLIRIS is used to treat patients with a
disease called Paroxysmal Nocturnal Hemoglobinuria (PNH), adults
and children with a disease called atypical Hemolytic Uremic
Syndrome (aHUS) (SOLIRIS is not for use in treating people with
Shiga toxin E. coli related hemolytic uremic syndrome [STEC-HUS]),
and adults with a disease called generalized Myasthenia Gravis
(gMG) who are anti-acetylcholine receptor (AchR) antibody positive.
It is not known if SOLIRIS is safe and effective in children with
PNH or gMG.
U.S. Important Safety Information for SOLIRIS®
(eculizumab)SOLIRIS is a medicine that affects the immune
system. SOLIRIS can lower the ability of the immune system to fight
infections. SOLIRIS increases the chance of getting serious and
life-threatening meningococcal infections. Meningococcal infections
may quickly become life-threatening and cause death if not
recognized and treated early.
Meningococcal vaccines must be received at least 2 weeks before
the first dose of SOLIRIS if one has not already had this vaccine.
If one’s doctor decided that urgent treatment with SOLIRIS is
needed, meningococcal vaccination should be administered as soon as
possible. If one has not been vaccinated and SOLIRIS therapy must
be initiated immediately, 2 weeks of antibiotics should also be
administered with the vaccinations. If one had a meningococcal
vaccine in the past, additional vaccination might be needed before
starting SOLIRIS. Call one’s doctor or get emergency medical care
right away if any of these signs and symptoms of a meningococcal
infection occur: headache with nausea or vomiting, headache and
fever, headache with a stiff neck or stiff back, fever, fever and a
rash, confusion, muscle aches with flu-like symptoms, and eyes
sensitive to light.
SOLIRIS is only available through a program called the SOLIRIS
REMS.
SOLIRIS may also increase the risk of other types of serious
infections. If one’s child is treated with SOLIRIS, make sure that
the child receives vaccinations against Streptococcus pneumoniae
and Haemophilus influenzae type b (Hib). Certain people may be at
risk of serious infections with gonorrhea. Talk to the doctor about
whether one is at risk for gonorrhea infection, about gonorrhea
prevention, and regular testing. Certain fungal infections
(Aspergillus) may also happen if one takes SOLIRIS and has a weak
immune system or a low white blood cell count.
Before one receives SOLIRIS, tell the doctor about all of the
medical conditions, including if one: has an infection or fever, is
pregnant or plans to become pregnant, and is breastfeeding or plans
to breastfeed. It is not known if SOLIRIS will harm an unborn baby.
It is not known if SOLIRIS passes into the breast milk.
Tell the doctor about all the medicines one takes, including
prescription and over-the-counter medicines, vitamins, and herbal
supplements. SOLIRIS and other medicines can affect each other
causing side effects.
It is important that one: has all recommended vaccinations
before starting SOLIRIS, receives 2 weeks of antibiotics if one
immediately starts SOLIRIS, and stays up-to-date with all
recommended vaccinations during treatment with SOLIRIS. Know the
medications one takes and the vaccines one receives. Keep a list of
them to show the doctor and pharmacist when one gets a new
medicine.
If one has PNH, the doctor will need to monitor closely for at
least 8 weeks after stopping SOLIRIS. Stopping treatment with
SOLIRIS may cause breakdown of the red blood cells due to PNH.
Symptoms or problems that can happen due to red blood cell
breakdown include: drop in the number of the red blood cell count,
drop in the platelet counts, confusion, kidney problems, blood
clots, difficulty breathing, and chest pain.
If one has aHUS, the doctor will need to monitor closely for at
least 12 weeks after stopping SOLIRIS for signs of worsening aHUS
symptoms or problems related to abnormal clotting (thrombotic
microangiopathy). Symptoms or problems that can happen with
abnormal clotting may include: stroke, confusion, seizure, chest
pain (angina), difficulty breathing, kidney problems, swellings in
arms or legs and a drop in platelet count.
SOLIRIS can cause serious side effects including serious
allergic reactions. Serious allergic reactions can happen during
one’s SOLIRIS infusion. Tell the doctor or nurse right away if one
gets any of these symptoms during the SOLIRIS infusion: chest pain,
trouble breathing or shortness of breath, swelling of the face,
tongue, or throat, and feeling faint or pass out. If one has an
allergic reaction to SOLIRIS, the doctor may need to infuse SOLIRIS
more slowly, or stop SOLIRIS. The most common side effects in
people with PNH treated with SOLIRIS include: headache, pain or
swelling of the nose or throat (nasopharyngitis), back pain, and
nausea. The most common side effects in people with aHUS treated
with SOLIRIS include: headache, diarrhea, high blood pressure
(hypertension), common cold (upper respiratory infection),
stomach-area (abdominal pain), vomiting, pain or swelling of the
nose or throat (nasopharyngitis), low red blood cell count
(anemia), cough, swelling of legs or feet (peripheral edema),
nausea, urinary tract infections, and fever. The most common side
effects in people with gMG treated with SOLIRIS include: muscle and
joint (musculoskeletal) pain.
Please see the accompanying full U.S. Prescribing Information
and Medication Guide for SOLIRIS, including Boxed WARNING regarding
serious and life-threatening meningococcal infections, also
available at: www.soliris.net.
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 two approved complement inhibitors to
treat patients with paroxysmal nocturnal hemoglobinuria (PNH) as
well as the first and only approved complement inhibitor to treat
atypical hemolytic uremic syndrome (aHUS) and anti-acetylcholine
receptor (AchR) antibody-positive generalized myasthenia gravis
(gMG), and is also developing it for patients with neuromyelitis
optica spectrum disorder (NMOSD). 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 several
mid-to-late-stage therapies, including a second complement
inhibitor, a copper-binding agent for Wilson disease and an
anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G
(IgG)-mediated diseases as well as several early-stage therapies,
including one for light chain (AL) amyloidosis and a second
anti-FcRn therapy. 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 that involve risks and uncertainties
relating to future events and the future performance of Alexion,
including statements related to: preventing relapses is the primary
goal of NMOSD treatment; the results of Phase 3 PREVENT study of
SOLIRIS® in adult patients with anti-aquaporin-4 (AQP4) auto
antibody-positive NMOSD provide hope for a promising new way of
treating patients with NMOSD; the impact that the relapse reduction
could have for patients with NMOSD using SOLIRIS; SOLIRIS may be a
promising new treatment for NMOSD; and future plans to present
additional results and findings from Phase 3 of the PREVENT Study.
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 anticipated benefits of SOLIRIS as a treatment for
NMOSD may not be realized; 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 failure to
receive (or meaning delay in receipt of) regulatory approval for
SOLIRIS as a treatment for NMOSD; the failure to deliver additional
information at conferences regarding clinical trials; 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 March 31, 2019
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
______________________________
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Flanagan EP et al. Epidemiology of
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Cabrera-Gomez JA et al. An epidemiological
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Alexion Pharmaceuticals, Inc.MediaArne Naeveke, PhD,
857-338-8597OrInvestorsSusan Altschuller, PhD, 857-338-8788
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