Soliris (eculizumab) has been approved in the European Union (EU) for expanded use to include the treatment of refractory generalised myasthenia gravis (gMG) in children and adolescents aged six to 17 years who are anti-acetylcholine receptor (AChR) antibody-positive (Ab+). This is the first and only targeted therapy approved for the treatment of paediatric patients with the disease in the EU.

The approval by the European Commission follows the positive opinion (https://www.astrazeneca.com/media-centre/press-releases/2023/soliris-recommended-for-approval-in-the-eu-by-chmp-for-children-and-adolescents.html) of the Committee for Medicinal Products for Human Use (CHMP) and is based on results from the Phase III trial of Soliris in paediatric patients with refractory gMG.[1 ]

In the trial, Soliris demonstrated clinical benefit in paediatric patients with refractory gMG who previously failed immunosuppressive treatment and continued to experience significant unresolved disease symptoms. Soliris showed significant improvement in the primary endpoint of change from baseline in Quantitative Myasthenia Gravis (QMG) total score at week 26, a physician-reported scale assessing disease severity and function (-5.8 [95% CI -8.4, -3.13], p<0.0004).[1]

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.[2 ]

John F. Brandsema, MD, Children's Hospital of Philadelphia and primary investigator in the Phase III trial of paediatric patients, said: "This approval represents a significant advance in care for paediatric patients with refractory gMG, who previously had no targeted treatment options to help manage their condition. Soliris showed clinical benefit and sustained improvements in disease severity through 26 weeks in a Phase III trial, offering potential to improve quality of life and redefine disease management for children and adolescents living with this rare neurological disease."

Marc Dunoyer, Chief Executive Officer, Alexion, said: "The impact of gMG on children can be devastating, and families have long been awaiting solutions. This approval of our first-in-class C5 inhibitor Soliris for paediatric patients with refractory gMG in the EU exemplifies our efforts to deliver transformative medicines that help address unmet medical needs for rare disease communities. Soliris offers hope for improved outcomes for children and adolescents impacted by gMG and we are committed to increasing access for these families as quickly as possible."

The efficacy and safety of Soliris in paediatric patients aged six years and older is consistent with the established profile of Soliris in clinical trials involving adults with refractory gMG.[1,3,4] In the Phase III clinical trial of paediatric patients, the majority of reported adverse events were considered mild or moderate. The most common adverse events were headache and nasopharyngitis.[1]

Soliris was first approved the EU in 2017 for the treatment of certain adults with gMG and is also approved for certain adults with gMG in the US, China and Japan. Regulatory submissions for Soliris for the treatment of paediatric patients with gMG are currently ongoing or planned with multiple health authorities.

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.[2,5-8] 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.[9-11] 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.[12,13]

Phase III Trial in Paediatric Patients with Refractory gMG
A Phase III open-label, multicentre 26-week trial evaluated the safety and efficacy of Soliris in eleven patients aged 12 to 17 years old. Participants were required to be older than six years of age, younger than 18, have a confirmed refractory myasthenia gravis diagnosis with a positive serologic test for anti-AChR antibodies, prior failure after a year or more on immunosuppressive therapy or required maintenance plasma exchange (PE) or intravenous immunoglobulin (IVIg) to control symptoms, Quantitative Myasthenia Gravis (QMG) score of at least 12 at trial entry and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening.[1,14]

The primary endpoint of change from baseline in QMG 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 Soliris, which is ongoing.

Soliris
Soliris (eculizumab) is a first-in-class 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 terminal complement cascade over-responds, leading the body to attack its own healthy cells. Soliris is administered intravenously every two weeks, following an introductory dosing period.

Soliris is approved in the US, EU, Japan and China for the treatment of patients with paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome.

Additionally, Soliris is approved in the EU for the treatment of certain paediatric patients with gMG, and in the US, Japan and China for certain adults with gMG.

Further, Soliris is approved in the US, EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder.

Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related haemolytic uraemic syndrome.

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 more than 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
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 (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

Contacts
For details on how to contact the Investor Relations Team, please click here (https://www.astrazeneca.com/investor-relations.html#Contacts). For Media contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html).

References

1. Brandsema JF, Ginsberg M, Hoshino H, et al. A phase 3, open-label, multicenter study to evaluate eculizumab in adolescents with refractory generalized myasthenia gravis. Oral Presentation at: American Academy of Neurology Annual Meeting, April 23, 2023; S5.009.
2. Howard JF. Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences 2017;1412(1), 113-128.
3. Howard JF, Utsugisawa K, Benetar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurology. 2017;16(12), 976-86.
4. Muppidi S, et al. Muscle Nerve. 2019;60(1):14-24. doi:10.1002/mus.26447.
5. Anil R, Kumar A, Alaparthi S, et al. 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.
6. Oh SJ. Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. Journal of Clinical Neurology. 2009;5(2):53-64.
7. Tomschik M, Hilger E, Rath J, et al. Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis. Neurology. 2020;95(10):e1426-e1436.
8. Hendricks TM, Bhatti MT, Hodge D, et al. Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019;205:99-105.
9. Myasthenia Gravis. National Organization for Rare Disorders (NORD). Available here (https://rarediseases.org/rare-diseases/myasthenia-gravis/). Accessed May 2023.
10. Howard JF, (2015). Clinical Overview of MG. Available here (https://myasthenia.org/Professionals/Clinical-Overview-of-MG). Accessed May 2023.
11. Sanders DB, Raja SM, Guptill JT, et al. The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve. 2020; 63(2), 209-216.
12. Myasthenia Gravis Fact Sheet. National Institutes of Neurological Disorders and Stroke. 2020. Available here (https://www.ninds.nih.gov/sites/default/files/migrate-documents/myasthenia_gravis_e_march_2020_508c.pdf). Accessed March 2022.
13. Ding J, Zhao S, Ren K, et al. Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology. 2020; 20(238).
14. ClinicalTrials.gov. A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG). NCT Identifier: NCT03759366. Available here (https://classic.clinicaltrials.gov/ct2/show/NCT03759366). Accessed May 2023.