– Study met primary endpoint of change from
baseline in the Myasthenia Gravis-Activities of Daily Living
Profile (MG-ADL) total score at Week 26 –
– ULTOMIRIS demonstrated compelling efficacy as
early as Week 1, sustained for 52 weeks –
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced
positive topline results from a Phase 3 study evaluating the safety
and efficacy of ULTOMIRIS® (ravulizumab-cwvz) in adults with
generalized myasthenia gravis (gMG). The study met, with high
statistical significance, its primary endpoint of change from
baseline in the Myasthenia Gravis-Activities of Daily Living
Profile (MG-ADL) total score, a patient-reported assessment, at
Week 26, and for the subset of patients who have completed 26 weeks
in the extension study to date, the positive treatment effect was
maintained through a total of 52 weeks. ULTOMIRIS was well
tolerated with a safety profile consistent with that observed in
Phase 3 studies in paroxysmal nocturnal hemoglobinuria (PNH) and
atypical hemolytic uremic syndrome (aHUS). Based on these results,
Alexion plans to make regulatory filings in the U.S., European
Union and Japan in late 2021/early 2022.
“The treatment landscape for people living with gMG has advanced
and expanded rapidly in recent years, empowering both patients and
caregivers. However, as a clinician and scientist, I know the work
is not done,” said Professor James F. Howard, M.D., Department of
Neurology at The University of North Carolina, Chapel Hill, USA,
and lead primary investigator in the Phase 3 study. “These Phase 3
ULTOMIRIS results reinforce the critical role complement inhibition
plays in treating gMG. I am encouraged by the opportunity this
could provide for more patients to be treated early with a
mechanism of action designed to preserve neuromuscular
function.”
“The approval of SOLIRIS was a critically important first step
in addressing the urgent need for a treatment for people with
severe symptoms and complications of MG, and was the first new
treatment for this devastating disease in more than 60 years.
Today’s results demonstrate that ULTOMIRIS may help a broader range
of patients than was studied in the SOLIRIS Phase 3 trial,
including those with milder symptoms or earlier in their treatment
journey, while still offering clinically meaningful benefits that
were seen as early as Week 1 and maintained up to 52 weeks,” said
John Orloff, M.D., Executive Vice President and Head of Research
& Development at Alexion. “These data provide confidence that
ULTOMIRIS has the potential to become the new standard of care for
gMG and may reduce patient burden with its less frequent dosing
schedule, leading to better treatment adherence and patient
satisfaction. We are working to prepare regulatory submissions in
the U.S., EU and Japan as quickly as possible.”
About the Phase 3 Study This global Phase 3 randomized,
double-blind, placebo-controlled, multicenter 26-week study
evaluated the safety and efficacy of ULTOMIRIS in adults with gMG
who were not previously treated with a complement inhibitor
medicine. The study enrolled 175 patients across North America,
Europe, Asia-Pacific and Japan. To enter the study, participants
were required to have a confirmed MG diagnosis at least 6 months
prior to the screening visit with a positive serologic test for
anti-AChR antibodies, MG-ADL total score of at least 6 at study
entry and Myasthenia Gravis Foundation of America (MGFA) Clinical
Classification Class II to IV at screening. There was no
requirement for prior treatment failure, and patients could stay on
stable standard of care medicines, with a few exceptions, for the
duration of the study.
Patients were randomized 1:1 to receive ULTOMIRIS or placebo for
a total of 26 weeks. Patients received a single weight-based
loading dose on Day 1, followed by regular weight-based maintenance
dosing beginning on Day 15, every 8 weeks. The primary endpoint of
change from baseline in the Myasthenia Gravis-Activities of Daily
Living Profile (MG-ADL) total score at Week 26 was assessed along
with multiple secondary endpoints evaluating improvement in
disease-related and quality of life measures.
The study met its primary endpoint, with a statistically
significant change in MG-ADL score from baseline through Week 26
for patients receiving ULTOMIRIS compared to those receiving
placebo (ULTOMIRIS: -3.1, placebo: -1.4, treatment difference:
-1.6, p<0.001).
In the prospectively-defined secondary endpoints of change from
baseline through Week 26 in Quantitative Myasthenia Gravis (QMG)
total score – a physician-administered assessment of MG clinical
severity – as well as the proportion of patients who achieved an
improvement of at least 5 points in QMG, ULTOMIRIS also
demonstrated clinically meaningful and statistically significant
improvements (p<0.001 and p=0.005, respectively). Nearly three
times as many patients receiving ULTOMIRIS experienced an
improvement of at least 5 points in their QMG score compared to
patients receiving placebo (30.0% vs 11.3%). These improvements in
MG-ADL and QMG scores were observed as early as Week 1 and were
sustained through Week 26.
Additional secondary endpoints assessing qualify of life
measures, such as Revised 15-Component Myasthenia Gravis Quality of
Life (MG-QOL15r) score (p=0.064) and Neuro-QOL Fatigue score
(p=0.373), did not meet statistical significance at Week 26. The
proportion of patients who achieved an improvement of at least 3
points in MG-ADL score (ULTOMIRIS: 56.7%, placebo: 34.1%, nominal
p=0.005), was not considered statistically significant based on
hierarchical testing.
During the randomized controlled period, adverse events were
comparable between the ULTOMIRIS and placebo groups. The most
frequently observed adverse events were headache (ULTOMIRIS: 18.6%;
placebo: 25.8%), diarrhea (ULTOMIRIS: 15.1%; placebo: 12.4%) and
nausea (ULTOMIRIS: 10.5%; placebo: 10.1%). The most frequently
observed serious adverse events were MG crisis (ULTOMIRIS: 1.2%)
and MG worsening (placebo: 3.4%).
Through 52 weeks (26 weeks randomized controlled period + 26
weeks of open-label extension), there were four patient deaths in
the ULTOMIRIS group – three of them were due to COVID-19 and none
were considered related to treatment with ULTOMIRIS. No cases of
meningococcal infection were observed through 52 weeks.
Patients who completed the randomized controlled period were
eligible to continue into an open-label extension period evaluating
the safety and efficacy of ULTOMIRIS for up to two years, which is
ongoing. At the time of this preliminary analysis of the open-label
extension period, 75 patients had completed 26 weeks of treatment,
for a total of 52 weeks of treatment. Among the patients who
received ULTOMIRIS in the randomized controlled period, the
treatment effects were maintained through an additional 26 weeks of
treatment, demonstrating sustained efficacy for a total of 52
weeks. In addition, patients who received placebo in the randomized
controlled period and switched to ULTOMIRIS at the beginning of the
open-label extension showed immediate and sustained improvement in
MG-ADL and QMG scores in a similar magnitude and time course to
that observed in the ULTOMIRIS group during the randomized
controlled period.
About Generalized Myasthenia Gravis Generalized
myasthenia gravis (gMG) is a rare autoimmune disorder characterized
by severe muscle weakness. In gMG, inflammation causes damage at
the connection point between nerve cells and the muscles they
control (known as the neuromuscular junction or NMJ). This damage
leads to a breakdown of communication between the brain and
muscles, causing loss of muscle function and severe weakness.
About 85 percent of people with gMG produce specific antibodies
that bind to the surface of the cells at the NMJ. This binding
activates the complement cascade and causes the immune system to
attack the NMJ. People with gMG can suffer from initial symptoms,
such as slurred speech, droopy eyelids, double vision, and lack of
balance, which can often lead to more severe symptoms like choking,
impaired swallowing, extreme fatigue and even episodes of
respiratory failure.
gMG can occur at any age, but it most commonly begins for women
before the age of 40 and for men after the age of 60. The
prevalence of gMG is estimated at 107 to 278 per million
people.
About ULTOMIRIS® ULTOMIRIS® (ravulizumab) is the first
and only long-acting C5 complement inhibitor. The medication works
by inhibiting the C5 protein in the terminal complement cascade, a
part of the body’s immune system. When activated in an uncontrolled
manner, the complement cascade over-responds, leading the body to
attack its own healthy cells. ULTOMIRIS is administered
intravenously every eight weeks or, for pediatric patients less
than 20 kg, every four weeks, following a loading dose. ULTOMIRIS
is approved in the United States for the treatment of adults and
children (one month of age and older) with paroxysmal nocturnal
hemoglobinuria (PNH), as well as in the European Union (EU) and
Japan as a treatment for adults with PNH. It is also approved in
the U.S. and Japan for atypical hemolytic uremic syndrome (aHUS) to
inhibit complement-mediated thrombotic microangiopathy (TMA) in
adult and pediatric (one month of age and older) patients, as well
as in the EU for the treatment of adults and children with a body
weight of at least 10 kg with aHUS. To learn more about the
regulatory status of ULTOMIRIS in the countries that we serve,
please visit www.alexion.com.
INDICATIONS & IMPORTANT SAFETY INFORMATION for ULTOMIRIS®
(ravulizumab-cwvz)
INDICATIONS What is ULTOMIRIS? ULTOMIRIS is a
prescription medicine used to treat:
- adults and children 1 month of age and older with a disease
called Paroxysmal Nocturnal Hemoglobinuria (PNH).
- adults and children 1 month of age and older with a disease
called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not
used in treating people with Shiga toxin E. coli related hemolytic
uremic syndrome (STEC-HUS).
It is not known if ULTOMIRIS is safe and effective in children
younger than 1 month of age.
IMPORTANT SAFETY INFORMATION What is the most important
information I should know about ULTOMIRIS? ULTOMIRIS is a medicine
that affects your immune system and can lower the ability of your
immune system to fight infections.
- ULTOMIRIS increases your chance of getting serious and
life-threatening meningococcal infections that may quickly become
life-threatening and cause death if not recognized and treated
early.
- You must receive meningococcal vaccines at least 2 weeks before
your first dose of ULTOMIRIS if you are not vaccinated.
- If your doctor decided that urgent treatment with ULTOMIRIS is
needed, you should receive meningococcal vaccination as soon as
possible.
- If you have not been vaccinated and ULTOMIRIS therapy must be
initiated immediately, you should also receive 2 weeks of
antibiotics with your vaccinations.
- If you had a meningococcal vaccine in the past, you might need
additional vaccination. Your doctor will decide if you need
additional vaccination.
- Meningococcal vaccines reduce but do not prevent all
meningococcal infections. Call your doctor or get emergency medical
care right away if you get any of these signs and symptoms of a
meningococcal infection: 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.
Your doctor will give you a Patient Safety Card about the
risk of meningococcal infection. Carry it with you at all times
during treatment and for 8 months after your last ULTOMIRIS dose.
It is important to show this card to any doctor or nurse to help
them diagnose and treat you quickly.
ULTOMIRIS is only available through a program called the
ULTOMIRIS REMS. Before you can receive ULTOMIRIS, your doctor
must: enroll in the ULTOMIRIS REMS program; counsel you about the
risk of meningococcal infection; give you information and a
Patient Safety Card about the symptoms and your risk of
meningococcal infection (as discussed above); and make sure that
you are vaccinated with a meningococcal vaccine, and if needed, get
revaccinated with the meningococcal vaccine. Ask your doctor if you
are not sure if you need to be revaccinated.
ULTOMIRIS may also increase the risk of other types of
serious infections. Make sure your child receives vaccinations
against Streptococcus pneumoniae and Haemophilis influenzae type b
(Hib) if treated with ULTOMIRIS. Call your doctor right away if you
have any new signs or symptoms of infection.
Who should not receive ULTOMIRIS? Do not receive
ULTOMIRIS if you have a meningococcal infection or have not been
vaccinated against meningococcal infection unless your doctor
decides that urgent treatment with ULTOMIRIS is needed.
Before you receive ULTOMIRIS, tell your doctor about all of
your medical conditions, including if you: have an infection or
fever, are pregnant or plan to become pregnant, and are
breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS
will harm your unborn baby or if it passes into your breast milk.
You should not breastfeed during treatment and for 8 months after
your final dose of ULTOMIRIS.
Tell your doctor about all the vaccines you receive and
medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements which could affect your
treatment.
If you have PNH and you stop receiving ULTOMIRIS, your doctor
will need to monitor you closely for at least 16 weeks after you
stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red
blood cells due to PNH. Symptoms or problems that can happen due to
red blood cell breakdown include: drop in your red blood cell
count, tiredness, blood in your urine,
stomach-area (abdomen) pain, shortness of breath,
blood clots, trouble swallowing, and erectile dysfunction
(ED) in males.
If you have aHUS, your doctor will need to monitor you
closely for at least 12 months after stopping treatment for signs
of worsening aHUS or problems related to a type of abnormal
clotting and breakdown of your red blood cells called thrombotic
microangiopathy (TMA). Symptoms or problems that can happen with
TMA may include: confusion or loss of consciousness, seizures,
chest pain (angina), difficulty breathing and blood clots or
stroke.
What are the possible side effects of ULTOMIRIS?
ULTOMIRIS can cause serious side effects including
infusion-related reactions. Symptoms of an infusion-related
reaction with ULTOMIRIS may include lower back pain, feeling faint
or discomfort in your arms or legs. Tell your doctor or nurse right
away if you develop these symptoms, or any other symptoms during
your ULTOMIRIS infusion that may mean you are having a serious
infusion reaction, including: chest pain, trouble breathing or
shortness of breath, swelling of your face, tongue, or throat, and
feel faint or pass out.
The most common side effects of ULTOMIRIS in people treated
for PNH are upper respiratory tract infection and headache.
The most common side effects of ULTOMIRIS in people with aHUS
are upper respiratory tract infection, diarrhea, nausea, vomiting,
headache, high blood pressure and fever.
Tell your doctor about any side effect that bothers you or that
does not go away. These are not all the possible side effects of
ULTOMIRIS. For more information, ask your doctor or pharmacist.
Call your doctor right away if you miss an ULTOMIRIS infusion or
for medical advice about side effects. You may report side effects
to FDA at 1-800-FDA-1088.
Please see the accompanying full Prescribing Information and
Medication Guide for ULTOMIRIS, including Boxed WARNING regarding
serious and life-threatening meningococcal
infections/sepsis.
About Alexion Alexion is a global biopharmaceutical
company focused on serving patients and families affected by rare
diseases and devastating conditions through the discovery,
development and commercialization of life-changing medicines. As a
leader in rare diseases for more than 25 years, Alexion has
developed and commercializes two approved complement inhibitors to
treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and
atypical hemolytic uremic syndrome (aHUS), as well as the first and
only approved complement inhibitor to treat anti-acetylcholine
receptor (AchR) antibody-positive generalized myasthenia gravis
(gMG) and 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)
as well as the first and only approved Factor Xa inhibitor reversal
agent. In addition, the company is developing several
mid-to-late-stage therapies, including a copper-binding agent for
Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for
rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D
inhibitor as well as several early-stage therapies, including one
for light chain (AL) amyloidosis, a second oral Factor D inhibitor
and a third complement inhibitor. Alexion focuses its research
efforts on novel molecules and targets in the complement cascade
and its development efforts on hematology, nephrology, neurology,
metabolic disorders, cardiology, ophthalmology and acute care.
Headquartered in Boston, Massachusetts, Alexion 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-P]
Forward-Looking Statements This press release contains
forward-looking statements that involve risks and uncertainties
relating to future events and the future performance of Alexion and
its products, including statements related to: the anticipated
benefits of ULTOMIRIS for gMG patients; Alexion plans to make
regulatory filings in the U.S., European Union and Japan in late
2021/early 2022; ULTOMIRIS has the opportunity to provide more
patients that are treated early with a mechanism of action designed
to preserve neuromuscular function; ULTOMIRIS may help a broader
range of patients than was studied in the SOLIRIS Phase 3 trial;
ULTOMIRIS has the potential to become the new standard of care for
gMG and may reduce patient burden with its less frequent dosing
schedule, leading to better treatment adherence and patient
satisfaction; and ULTOMIRIS’ continued safety and efficacy
profile.
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: ULTOMIRIS may not be approved for use by regulatory
agencies (or such approval may be delayed); the filing of requests
for regulatory approval may not ultimately be submitted (or may be
delayed); ULTOMIRIS may not generate the expected benefits to
patients (or the healthcare system) that are anticipated;
anticipated regulatory approvals may be delayed or refused; the
Company may experience delays (or be prevented) for obtaining
approval or commencing or continuing sales of ULTOMIRIS for gMG,
due to manufacturing or other reasons; results of clinical trials
may not be sufficient to satisfy regulatory authorities to approve
ULTOMIRIS as a treatment for gMG and/or other indication (or they
may request additional trials or additional information); results
in clinical trials may not be indicative of results from later
stage or larger clinical trials (or the use in broader patient
populations once the product is approved for use by regulatory
agencies); the possibility that results of clinical trials are not
predictive of safety and efficacy and potency of our products
including ULTOMIRIS (or we fail to adequately operate or manage our
clinical trials) which could cause us to discontinue sales of the
product (or halt trials, delay or prevent us from making regulatory
approval filings or result in denial of approval of our product
candidates); the severity of the impact of the COVID-19 pandemic on
Alexion’s business, including on commercial and clinical trial and
clinical development programs; unexpected delays in clinical
trials; unexpected concerns regarding products and product
candidates that may arise from additional data or analysis obtained
during clinical trials or obtained once used by patients following
product approval; future product improvements may not be realized
due to expense or feasibility or other factors; delays (expected or
unexpected) in the time it takes regulatory agencies to review and
make determinations on applications for the marketing approval of
our products; inability to timely submit (or failure to submit)
future applications for regulatory approval for our products and
product candidates; inability to timely initiate (or failure to
initiate) and complete future clinical trials due to safety issues,
IRB decisions, CMC-related issues, expense or unfavorable results
from earlier trials (among other reasons); our dependence on sales
from our complement inhibitors; future competition from biosimilars
and novel products; decisions of regulatory authorities regarding
the adequacy of our research, marketing approval or material
limitations on the marketing of our products; delays or the
inability to launch product candidates due to regulatory
restrictions, anticipated expense, manufacturing issues, or other
matters; interruptions or failures in the manufacture and supply of
our products and our product candidates; failure to satisfactorily
address matters raised by regulatory agencies regarding products
and product candidates; uncertainty of long-term success in
developing, licensing or acquiring other product candidates or
additional indications for existing products; the possibility that
current rates of adoption of our products are not sustained; the
adequacy of our pharmacovigilance and drug safety reporting
processes; failure to protect and enforce our data, intellectual
property and proprietary rights and the risks and uncertainties
relating to intellectual property claims, lawsuits and challenges
against us (including intellectual property lawsuits relating to
ULTOMIRIS brought by third parties); the risk that third party
payors (including governmental agencies) will not reimburse or
continue to reimburse for the use of our products at acceptable
rates or at all; failure to realize the benefits and potential of
investments, collaborations, licenses and acquisitions; the
possibility that expected tax benefits will not be realized;
potential declines in sovereign credit ratings or sovereign
defaults in countries where we sell our products; delay of
collection or reduction in reimbursement due to adverse economic
conditions or changes in government and private insurer regulations
and approaches to reimbursement; adverse impacts on our supply
chain, clinical trials, manufacturing operations, financial
results, liquidity, hospitals, pharmacies and health care systems
from natural disasters and global pandemics, including the
coronavirus; uncertainties surrounding legal proceedings, company
investigations and government investigations; the risk that
estimates regarding the number of patients with PNH, aHUS, gMG,
NMOSD, HPP and LAL-D and other indications we are pursuing are
inaccurate; the impact of the proposed transaction between Alexion
and AstraZeneca plc; the risks of changing foreign exchange rates;
risks relating to the potential effects of the Company's
restructurings; 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 quarter ended March 31, 2021 and in our 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210715006015/en/
Media Lisa Taylor, 857-338-9025 Senior Director,
Corporate Communications
Investors Kevin O’Neil, (857) 338-8505 Associate
Director, Investor Relations
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