First and only long-acting C5 complement inhibitor showed early effect and demonstrated clinical improvement in activities of daily living.
Ultomiris (ravulizumab) has been recommended for marketing authorisation in the
In this 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.1
gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.2 The diagnosed prevalence of gMG in the EU is estimated at approximately 89,000.3-9
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 drug reactions are diarrhoea, upper respiratory tract infection, nasopharyngitis and headache.1
The CHMP recommended approval as an add-on to standard therapy for the treatment of adult patients with gMG who are AChR antibody-positive.
Ultomiris was approved in the US for adults with gMG who are AChR antibody-positive in
Notes
gMG
gMG is a rare autoimmune disorder characterised by loss of muscle function and severe muscle weakness.2
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.2,4,5,10,11 This binding activates the complement system, which is essential to the body's defence against infection, causing the immune system to attack the NMJ.2 This leads to inflammation and a breakdown in communication between the brain and the muscles.2
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
CHAMPION-MG
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
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
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 for the treatment of certain adults with gMG.
Ultomiris is also approved in the US, EU and
Additionally, Ultomiris is approved in the US, EU and
As part of a broad development programme, Ultomiris is being assessed for the treatment of additional haematology and neurology indications.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within
Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.
References
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Howard, J. F., (2017). Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of
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Sweden 2006-2016. Brain Behav. 2020;10:e01819. https://doi.org/10.1002/brb3.1819 -
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Oh SJ., (2009). Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status.
Journal of Clinical Neurology . 2009bJun 1 ;5(2):53-64. - 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; 277:594-604.
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Lefter, S., Hardiman, O., Ryan, A., (2017). A population-based epidemiologic study of adult neuromuscular disease in the
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Pallaver, F., Riviera, AP., Piffer, S., Ricciardi, R., Roni, R., Orrico, D., Bonifati, DM., (2011). Change in Myasthenia Gravis Epidemiology in
Trento, Italy , after Twenty Years. Neuroepidemiology 2011;36:282-287. -
Santos, E., Coutinho, E., Moreira, I., et.al., (2016). Epidemiology of Myasthenia Gravis in
Northern Portugal : Frequency Estimates and Clinical Epidemiological Distribution of Cases. Muscle Nerve 2016; 54: 413-421. -
Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M., Cetin, H., Löscher, 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.
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Myasthenia Gravis.
National Organization for Rare Disorders (NORD). Available here. AccessedMarch 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.
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Myasthenia Gravis Fact Sheet. (2020,
April 27 ).National Institutes of Neurological Disorders and Stroke . Available here. AccessedMarch 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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