New England Journal of Medicine Publishes Positive Phase 3 PREVENT Data for SOLIRIS® (eculizumab) in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)
May 3, 2019
– 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 –
BOSTON & PHILADELPHIA–(BUSINESS WIRE)–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* |
||||||
|
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 Study
The 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 NMOSD
Neuromyelitis 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 Alexion
Alexion 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 Statement
This 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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Contacts
Alexion Pharmaceuticals, Inc.
Media
Arne Naeveke, PhD,
857-338-8597
Or
Investors
Susan Altschuller, PhD,
857-338-8788