-- 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) --
Alexion 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 population.”
About the Open-Label Extension Study (ECU-MG-302)94%
(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 worst-rank
analysis.
The REGAIN study (ECU-MG-301) and its open-label extension study
(ECU-MG-302) are sponsored by Alexion.
About Generalized Myasthenia GravisMyasthenia 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
life-threatening.2,3,8
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 plasmapheresis (PLEX).
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
Treatment).
For more information on SOLIRIS, please see full Prescribing
Information for SOLIRIS, including BOXED WARNING regarding risk of
serious meningococcal infections, available at www.soliris.net.
Important SOLIRIS Safety InformationSOLIRIS 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 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 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.
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 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.
References:
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. 2013;48(1):76-84.
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.
2009;8(5):475-490.
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.
2011;37(2):136-143.
11Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia
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Alexion Pharmaceuticals, Inc.MediaDeaidra Smith,
Deaidra.Smith@alexion.comDirector, Portfolio and Country
Communications
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