First and only long-acting C5 complement
inhibitor to demonstrate clinical improvement in patients with
generalized myasthenia gravis
ULTOMIRIS showed early effect and lasting
improvement in activities of daily living and has potential to
reduce treatment burden with dosing every 8 weeks
ULTOMIRIS® (ravulizumab-cwvz) has been approved in the US for
the treatment of adult patients with generalized myasthenia gravis
(gMG) who are anti-acetylcholine receptor (AChR) antibody-positive,
which represents 80% of people living with the disease.1-5
The approval by the Food and Drug Administration (FDA) was based
on positive results from the CHAMPION-MG Phase III trial, in which
ULTOMIRIS was superior to placebo in the primary endpoint of change
from baseline in the Myasthenia Gravis-Activities of Daily Living
Profile (MG-ADL) total score at Week 26, a patient-reported scale
that assesses patients’ abilities to perform daily activities.1
This FDA action marks the first and only approval for a
long-acting C5 complement inhibitor for the treatment of gMG.
gMG is a rare, debilitating, chronic, autoimmune neuromuscular
disease that leads to a loss of muscle function and severe
weakness.6 The diagnosed prevalence of gMG in the US is estimated
at approximately 90,000.7
Professor James F. Howard, Jr, MD, Department of Neurology at
The University of North Carolina School of Medicine and lead
primary investigator in the CHAMPION-MG trial said: “Despite recent
advances, managing gMG is complex. Earlier intervention can
preserve function and quality of life. This approval offers
patients, including those with milder symptoms, a long-acting C5
inhibitor with early onset and reliable efficacy.”
Samantha Masterson, Chief Executive Officer, Myasthenia Gravis
Foundation of America (MGFA), said: “gMG takes a physical and
emotional toll on those living with the disease. We are grateful
for continued innovation and research into new treatment and dosing
options to meet the needs of more patients and reduce the treatment
burden. With the approval of ULTOMIRIS, we’re excited that MG
patients now have another option to consider as part of their
personalized treatment strategies that may offer more convenience
and improve muscle weakness.”
Marc Dunoyer, Chief Executive Officer, Alexion, said: “Since
bringing forward the first complement inhibitor, we’ve continued to
listen to the community and focused innovation on the needs of gMG
patients. We’re proud to deliver on this commitment with today’s
approval. ULTOMIRIS, the only long-acting C5 inhibitor, will
benefit a broader range of patients, including those with milder
symptoms. As presented at the 2022 American Academy of Neurology
Annual Meeting, ULTOMIRIS has demonstrated clinical benefit through
60 weeks, with treatment every eight weeks, compared to SOLIRIS
every two weeks.”
In the trial, the safety profile of ULTOMIRIS was comparable to
placebo and consistent with that observed in Phase III trials of
ULTOMIRIS in paroxysmal nocturnal hemoglobinuria (PNH) and atypical
hemolytic uremic syndrome (aHUS). The most common adverse reactions
in patients receiving ULTOMIRIS were upper respiratory tract
infection and diarrhea.1
Results from the CHAMPION-MG trial were recently published
online in NEJM Evidence and presented at the 2022 American Academy
of Neurology Annual Meeting in April.
Regulatory submissions for ULTOMIRIS for the treatment of gMG
are currently under review with multiple health authorities,
including in the European Union (EU) and Japan.
INDICATION(S) & IMPORTANT SAFETY INFORMATION for
ULTOMIRIS® (ravulizumab-cwvz)
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).
- adults with a disease called generalized myasthenia gravis
(gMG) who are anti-acetylcholine receptor (AChR) antibody
positive.
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, tiredness,
feeling faint, discomfort in your arms or legs, or bad taste. 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.
The most common side effects of ULTOMIRIS in people with gMG
are diarrhea and upper respiratory tract infection.
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.
Notes
gMG
gMG is a rare autoimmune disorder characterized by loss of
muscle function and severe muscle weakness.6
Eighty percent of people with gMG are AChR antibody positive
meaning they produce specific antibodies (anti-AChR) that bind to
signal receptors at the neuromuscular junction (NMJ), the
connection point between nerve cells and the muscles they control.
2-6 This binding activates the complement system, which is
essential to the body’s defense against infection, causing the
immune system to attack the NMJ.6 This leads to inflammation and a
breakdown in communication between the brain and the muscles.6
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 60.8-10 Initial
symptoms may include slurred speech, double vision, droopy eyelids
and lack of balance; these can often lead to more severe symptoms
as the disease progresses such as, impaired swallowing, choking,
extreme fatigue and respiratory failure.11-12
CHAMPION-MG
The global Phase III randomized, double-blind,
placebo-controlled, multicenter 26-week trial evaluated the safety
and efficacy of ULTOMIRIS in adults with gMG. The trial enrolled
175 patients across North America, Europe, Asia-Pacific and Japan.
Participants were required to have a confirmed myasthenia gravis
diagnosis at least six months prior to the screening visit with a
positive serologic test for anti-AChR antibodies, MG-ADL total
score of at least 6 at trial entry and Myasthenia Gravis Foundation
of America Clinical Classification Class II to IV at screening.
Patients could stay on stable standard of care medicines, with a
few exceptions, for the duration of the randomized control
period.13
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 eight weeks. The primary endpoint
of change from baseline in the MG-ADL total score at Week 26 was
assessed along with multiple secondary endpoints evaluating
improvement in disease-related and quality-of-life measures.
Patients who completed the randomized control period were
eligible to continue into an open-label extension period evaluating
the safety and efficacy of ULTOMIRIS, which is ongoing.
ULTOMIRIS
ULTOMIRIS (ravulizumab-cwvz), the first and only long-acting C5
complement inhibitor, offers immediate, complete and sustained
complement inhibition. 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 in adult patients, following a loading dose.
ULTOMIRIS is approved in the US for the treatment of certain
adults with gMG.
ULTOMIRIS is also approved in the US, EU and Japan for the
treatment of certain adults and children with PNH.
Additionally, ULTOMIRIS is approved in the US, EU and Japan for
certain adults and children with aHUS to inhibit
complement-mediated thrombotic microangiopathy.
As part of a broad development program, ULTOMIRIS is being
assessed for the treatment of additional hematology and neurology
indications.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within
AstraZeneca focused on rare diseases, created following the 2021
acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare
diseases for nearly 30 years, Alexion is focused on serving
patients and families affected by rare diseases and devastating
conditions through the discovery, development and commercialization
of life-changing medicines. 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 and ophthalmology. Headquartered in Boston,
Massachusetts, Alexion has offices around the globe and serves
patients in more than 50 countries. For more information, please
visit www.alexion.com.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines in Oncology, Rare Diseases and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References
- Ultomiris (ravulizumab-cwvz) US prescribing information;
2022.
- Anil, R., Kumar, A., Alaparthi, S., Sharma, A., Nye, JL., Roy,
B., O’Connor, KC., Nowak, R., (2020). Exploring outcomes and
characteristics of myasthenia gravis: Rationale, aims and design of
registry - The EXPLORE-MG registry. J Neurol Sci. 2020 Jul
15;414:116830.
- Oh SJ., (2009). Muscle-specific receptor tyrosine kinase
antibody positive myasthenia gravis current status. Journal of
Clinical Neurology. 2009b Jun 1;5(2):53-64.
- Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M.,
Cetin, H., L�scher, W., Zimprich, F., (2020). Subgroup
stratification and outcome in recently diagnosed generalized
myasthenia gravis. Neurology. 2020 Sep 8;95(10):e1426-e1436.
- Hendricks, TM., Bhatti, MT., Hodge, D., Chen, J., (2019).
Incidence, Epidemiology, and Transformation of Ocular Myasthenia
Gravis: A Population-Based Study. Am J Ophthalmol. 2019
Sep;205:99-105.
- Howard, J. F., (2017). Myasthenia gravis: the role of
complement at the neuromuscular junction. Annals of The New York
Academy of Sciences, 1412(1), 113-128.
- Westerberg, E., Punga, A., (2020). Epidemiology of Myasthenia
Gravis in Sweden 2006–2016. Brain and behavior. 2020
Nov;10(11):e01819.
- Myasthenia Gravis. National Organization for Rare Disorders
(NORD). Available here. Accessed March 2022.
- Howard, J. F., (2015). Clinical Overview of MG. Available here.
Accessed March 2022.
- Sanders, D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L. D.,
Juel, V. C., & Massey, J. M., (2020). The Duke myasthenia
gravis clinic registry: I. Description and demographics. Muscle
& Nerve, 63(2), 209-216.
- Myasthenia Gravis Fact Sheet. (2020, April 27). National
Institutes of Neurological Disorders and Stroke. Available here.
Accessed March 2022.
- Ding, J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F., Zhang,
M., Li, Z., & Guo, J., (2020). Prediction of generalization of
ocular myasthenia gravis under immunosuppressive therapy in
Northwest China. BMC Neurology, 20(238).
- ClinicalTrials.gov. Safety and Efficacy Study of Ravulizumab in
Adults With Generalized Myasthenia Gravis. NCT Identifier:
NCT03920293. Available here. Accessed March 2022.
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