— New data suggest positive impact on clinical burden and sustained
long-term clinical benefit for adult patients with anti-acetylcholine
receptor (AChR) antibody-positive refractory generalized myasthenia
gravis (gMG) —
Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the publication
of data from an interim analysis of the Phase 3 open-label extension
study (ECU-MG-302) of REGAIN (ECU-MG-301) evaluating the long-term
efficacy and safety of SOLIRIS® (eculizumab) for the treatment of adult
patients with anti-acetylcholine receptor (AChR) antibody-positive
refractory generalized myasthenia gravis (gMG). Published in Muscle &
Nerve, the results indicate that the improvements demonstrated
during the initial six-month duration of the double-blinded Phase 3
REGAIN trial, were sustained over a treatment period of three years.
Additionally, patients who had previously been treated with placebo in
REGAIN showed rapid and significant improvement upon starting treatment
with SOLIRIS in the open-label extension (OLE).
“Symptom persistence is a major challenge in the treatment of gMG,” said
Srikanth Muppidi, M.D., Clinical Associate Professor, Department of
Neurology and Neurosciences at Stanford University School of Medicine.
“These results confirm that treatment with SOLIRIS can provide patients
with anti-AChR antibody-positive gMG adult patients with tangible and
durable clinical benefits and can help to reduce the burden of this
devastating disease on patients and their families.”
At the time of data analysis more than 55% of patients enrolled in the
OLE showed clinically meaningful response, based on the MG-Activities of
Daily Living scale (MG-ADL), and the majority of patients (56%) achieved
minimal manifestations or pharmacological remission.
The data from the OLE also confirm that the safety profile of SOLIRIS,
when used to treat patients with anti-AChR antibody-positive gMG, is
consistent with its safety profile seen in REGAIN. No cases of
meningococcal infection were reported by the interim data cut-off [one
case, which was resolved with antibiotic treatment, occurred after this
date], and the most common adverse events were headache (37.6% of
patients) and nasopharyngitis (31.6%). The most common serious adverse
event was myasthenia gravis worsening (12.8% of patients). When compared
with data from the year prior to the start of REGAIN, patients in the
OLE experienced significant reductions in rates of exacerbations (75%
reduction) and hospitalization (83% reduction).
Data reported in this interim analysis were based on results from 117
patients who received SOLIRIS (1,200 mg, every 2 weeks) for a median
duration of almost two years (22.7 months). Patients enrolled in the OLE
received SOLIRIS for a maximum of four years. Symptom improvement was
evaluated with multiple assessment tools, including the MG-ADL, the
Quantitative MG scale (QMG), the MG Composite scale (MGC) and the
15-item MG Quality of Life questionnaire (MG-QOL 15).
“As the first FDA-approved treatment for gMG in more than 60 years,
SOLIRIS represents an important option for adult patients with anti-AChR
antibody-positive gMG who previously experienced persistent symptoms and
significant morbidities despite previous therapy,” said José Menoyo,
M.D., Vice President, U.S. Medical Affairs at Alexion. “We hope that
this analysis of our open-label extension study contributes to the
overall understanding of the burden of disease and provides confidence
in the safety and benefit of long-term SOLIRIS treatment for this
About the Open-Label Extension Study (ECU-MG-302)
(117/125) of patients who completed the REGAIN study enrolled in the
open-label extension, of which 56 continued to receive SOLIRIS
(SOLIRIS/SOLIRIS group) and 61 were switched from placebo to SOLIRIS
(placebo/SOLIRIS group) within two weeks of completing the REGAIN study.
Patients were not informed of prior treatment assignment in REGAIN
through a four-week blinded induction phase, after which all patients
received ongoing open-label treatment with SOLIRIS (1,200 mg/dose) every
two weeks. For this interim analysis, 49 patients in the SOLIRIS/SOLIRIS
group and 56 patients in the placebo/SOLIRIS group completed week 26
assessments; 49 patients in the SOLIRIS/SOLIRIS group and 54 patients in
the placebo/SOLIRIS group completed week 52 assessments; and 47 patients
in the SOLIRIS/SOLIRIS group and 49 patients in the placebo/SOLIRIS
group completed week 78 assessments. Mean scores over time were
calculated using repeated measures from baseline. The study was
completed in January 2019.
About REGAIN (ECU-MG-301)
This was a randomized,
double-blind, placebo-controlled, multicenter Phase 3 clinical study
that evaluated the efficacy and safety of SOLIRIS over 26 weeks in 125
patients with a confirmed diagnosis of refractory gMG with positive
serologic test for antibodies against AChR. Patients initially received
900 mg of SOLIRIS or placebo weekly for 4 weeks followed by 1,200 mg of
SOLIRIS or placebo 1 week later, and then 1,200 mg of SOLIRIS or placebo
every 2 weeks. The primary efficacy endpoint of change from baseline in
MG-ADL total score at week 26, as well as the three secondary endpoints
—changes from baseline in QMG, MGC, and MG-QOL 15—were assessed using a
The REGAIN study (ECU-MG-301) and its open-label extension study
(ECU-MG-302) are sponsored by Alexion.
About Generalized Myasthenia Gravis
Myasthenia gravis (MG)
is a debilitating, chronic and progressive autoimmune neuromuscular
disease that can occur at any age but most commonly begins for women
before the age of 40 and men after the age of 60.1-4 It
typically begins with weakness in the muscles that control the movements
of the eyes and eyelids, and often progresses to the more severe and
generalized form, known as gMG, with weakness of the head, neck, trunk,
limb and respiratory muscles.4
While most patients with gMG can be managed with current therapies for
MG, 10-15% of patients fail to respond adequately to or cannot tolerate
multiple therapies for MG and continue to suffer profound muscle
weakness, and severe disease symptoms that limit function.5,6,7 These
patients can suffer from slurred speech, choking, impaired swallowing,
double or blurred vision, disabling fatigue, immobility requiring
assistance, shortness of breath, and episodes of respiratory failure.
Complications, exacerbations and myasthenic crises can require hospital
and intensive care unit admissions with prolonged stays and can be
In patients with anti-AChR antibody-positive MG, the body’s own immune
system turns on itself to produce antibodies against AChR, a receptor
located on muscle cells at the neuromuscular junction (NMJ) and used by
nerve cells to communicate with the muscles these nerves control.2,3 The
binding of these antibodies to AChR activates the complement cascade,
another part of the immune system, which leads to a localized
inflammation and destruction of the muscle membrane at the NMJ.9-11 As
a result, the communication between nerve and muscle is impaired, which
in turn leads to a loss of normal muscle function.2,3
Patients with anti-AChR antibody-positive gMG who continue to suffer
from severe disease symptoms and complications despite current therapies
for MG represent approximately 5-10% of all patients with MG.1-4
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.
When activated in an uncontrolled manner, complement 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 generalized
myasthenia gravis (gMG). 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. for the treatment of adult patients
with generalized MG (gMG) who are anti-AChR antibody-positive, in the EU
as the first and only 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
SOLIRIS has received Orphan Drug Designation (ODD) as a treatment for
patients with PNH in the U.S., EU, Japan and many other countries, as a
treatment for patients with aHUS in the U.S., EU, and many other
countries, as a treatment for patients with MG in the U.S. and EU, as a
treatment for patients with refractory gMG in Japan and as a treatment
for 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
Important SOLIRIS Safety Information
SOLIRIS is a
prescription medicine called a monoclonal antibody. SOLIRIS is used to
treat patients with a disease called Paroxysmal Nocturnal Hemoglobinuria
(PNH). SOLIRIS is also used to treat 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). SOLIRIS is also approved to treat 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.
SOLIRIS is a medicine that affects the immune system. SOLIRIS can lower
the ability of your 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
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
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 your platelet counts, confusion,
kidney problems, blood clots, difficulty breathing, and chest pain.
If one has aHUS, the doctor will need to monitor closely during and for
at least 12 weeks after stopping treatment 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, a drop
in the 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 feel
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;
fever. The most common side effects in people with gMG treated with
SOLIRIS include: muscle and joint (musculoskeletal) pain.
Please see the accompanying full
Prescribing Information and Medication
Guide for SOLIRIS, including Boxed WARNING regarding serious and
life-threatening meningococcal infections, available at: www.soliris.net.
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 anti-aquaporin-4 (AQP4) auto antibody-positive
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. 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.
1Huda R, Tüzün E, Christadoss P. Targeting complement system
to treat myasthenia gravis. Rev. Neurosci. 2014; 25(4): 575–583.
2Howard JF, Barohn RJ, Cutter GR et al. A randomized,
double-blind, placebo-controlled phase II study of eculizumab in
patients with refractory generalized myasthenia gravis. Muscle Nerve.
3National Institute of Neurological Disorders and Stroke.
Myasthenia Gravis Fact Sheet. Publication date May 2017. http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm.
4Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis:
emerging clinical and biological heterogeneity. Lancet Neurol.
5Silvestri N, Wolfe G. Treatment-refractory myasthenia
gravis. J. Clin Neuromuscul Dis. 2014;15(4):167-178.
6Howard J. Targeting the Complement System in Refractory
Myasthenia Gravis. Supplement to Neurology Reviews. February 2016.
7Sanders DB, Wolfe, GI, Benatar M, et al. International
consensus guidance for management of myasthenia gravis: Executive
summary. Neurology. 2016;87(4):419-25.
8Sathasivam S. Diagnosis and management of myasthenia gravis.
Progress in Neurology and Psychiatry. January/February 2014.
9Conti-Fine, et al. Myasthenia gravis: past, present, and
future. J Clin Invest. 2006; 116:2843-2354.
10Tüzün E, Huda R, Christadoss P. Complement and cytokine
based therapeutic strategies in myasthenia gravis. J Autoimmun.
11Meriggioli MN, Sanders DB. Muscle autoantibodies in
myasthenia gravis: beyond diagnosis? Expert Rev. Clin. Immunol.
Alexion Pharmaceuticals, Inc.
Deaidra Smith, Deaidra.Smith@alexion.com
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