RNS Number : 4292A
23 September 2022
23 September 2022 07:00 BST
Ultomiris approved in Europe for the treatment of adults with
generalised myasthenia gravis
First and only long-acting C5 inhibitor has demonstrated early
onset and sustained clinical benefit, and may reduce treatment
burden with dosing every 8 weeks
Improvement in activities of daily living seen across broad
range of patients, including those with milder symptoms
Ultomiris (ravulizumab) has been approved in Europe as an add-on
to standard therapy for the treatment of adult patients with
generalised myasthenia gravis (gMG) who are anti-acetylcholine
receptor (AChR) antibody-positive.
This decision marks the first and only approval for a
long-acting C5 complement inhibitor for the treatment of gMG in
Europe. gMG is a rare, debilitating, chronic, autoimmune
neuromuscular disease that leads to a loss of muscle function and
severe weakness.(1) The diagnosed prevalence of gMG in the EU is
estimated at approximately 89,000.(2-8)
The approval by the European Commission follows the positive
opinion of the Committee for Medicinal Products for Human Use and
is based on results from the CHAMPION-MG Phase III trial, which
were published online in NEJM Evidence. In the trial, 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.(9)
Additionally, in prolonged follow-up results from the open-label
extension, clinical benefit of Ultomiris was observed through 60
Renato Mantegazza, Professor at the Department of
Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS
Istituto Neurologico Carlo Besta, Milan, Italy, and CHAMPION-MG
trial investigator, said: "As physicians, we see first-hand how gMG
can have a debilitating impact on quality of life. Today's approval
is a major advancement for treating gMG in Europe, offering
patients and physicians a new, long-acting treatment option which
has shown reliable efficacy and sustained improvements in
activities of daily living."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "This
approval in Europe of the first and only long-acting C5 inhibitor
is an important step towards realising our vision of improving the
lives of people living with gMG and increasing access to Ultomiris
worldwide. Alexion's pioneering leadership in complement science
has affirmed C5 inhibition as a proven approach for managing this
debilitating disease. We're proud to offer a new treatment option
that provides more convenience in dosing and has shown clinical
benefit in a broader range of patients, including those who remain
symptomatic despite their initial standard of care treatment."
In CHAMPION-MG, the safety profile of Ultomiris was comparable
to placebo and consistent with that observed in Phase III trials of
Ultomiris in paroxysmal nocturnal haemoglobinuria (PNH) and
atypical haemolytic uraemic syndrome (aHUS). The most common
adverse reactions in patients receiving Ultomiris were diarrhoea,
upper respiratory tract infection, nasopharyngitis and
Ultomiris was approved in the US in April 2022 and Japan in
August 2022 for certain adults with gMG. Regulatory reviews are
ongoing in additional countries.
gMG is a rare autoimmune disorder characterised by loss of
muscle function and severe muscle weakness.(1)
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.(1,3,4,10,11) This binding activates the complement system,
which is essential to the body's defence against infection, causing
the immune system to attack the NMJ.(1) This leads to inflammation
and a breakdown in communication between the brain and the
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.(12-14)
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.(15,16)
The global Phase III randomised, double-blind,
placebo-controlled, multicentre 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 randomised control
Patients were randomised 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 randomised control period were
eligible to continue into an open-label extension period evaluating
the safety and efficacy of Ultomiris, which is ongoing.
Ultomiris (ravulizumab), 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, EU and Japan for the treatment
of certain adults with gMG.
Ultomiris is also approved in the US, EU and Japan for the
treatment of certain adults with PNH and for certain children with
PNH in the US and EU.
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 programme, Ultomiris is being
assessed for the treatment of additional haematology and neurology
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
commercialisation of life-changing medicines. Alexion focuses its
research efforts on novel molecules and targets in the complement
cascade and its development efforts on haematology, 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.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation 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. Please visit astrazeneca.com and follow the
Company on Twitter @AstraZeneca .
For details on how to contact the Investor Relations Team,
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1. 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.
2. Westerberg E, Punga AR. Epidemiology of Myasthenia Gravis in Sweden 2006-2016. Brain Behav. 2020;10:e01819. https://doi.org/10.1002/brb3.1819
3. 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
4. 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.
5. Fang, F., Sveinsson O., Thormar G., Granqvist M., Askling J.,
Lundberg IE., Ye W., (2015). The autoimmune spectrum of myasthenia
gravis: a Swedish population-based study. J Intern Med 2015;
6. Lefter, S., Hardiman, O., Ryan, A., (2017). A
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9. Ultomiris, European Product Information, September 2022.
10. Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M.,
Cetin, H., Löscher, W., Zimprich, F., (2020). Subgroup
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Incidence, Epidemiology, and Transformation of Ocular Myasthenia
Gravis: A Population-Based Study. Am J Ophthalmol. 2019
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(NORD). Available here . Accessed March 2022.
13. Howard, J. F., (2015). Clinical Overview of MG. Available
here . Accessed March 2022.
14. Sanders, D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L.
D., Juel, V. C., & Massey, J. M., (2020). The Duke myasthenia
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& Nerve, 63(2), 209-216.
15. Myasthenia Gravis Fact Sheet. (2020, April 27). National
Institutes of Neurological Disorders and Stroke. Available here .
Accessed March 2022.
16. Ding, J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F.,
Zhang, M., Li, Z., & Guo, J., (2020). Prediction of
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17. 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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