Ultomiris® approved in Canada for adults with generalized myasthenia gravis (gMG)

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

TORONTO, Jan. 17, 2023 /CNW/ - Ultomiris (ravulizumab) has been approved in Canada for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.¹ [PM, p.4A]

The approval by Health Canada was based on positive results from the CHAMPION-MG Phase III trial, in which Ultomiris was superior to placebo for 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 [PM p43A]

The Health Canada approval marks the first and only approval in Canada for a long-acting C5 complement inhibitor for the treatment of gMG.

Stacey Lintern, the CEO of Muscular Dystrophy Canada said, "Continued innovation and research is the most potent tactic we have against the significant treatment burden that gMG puts on those affected by this neuromuscular disorder. We're excited about the approval of Ultomiris and for the possibility of a new and promising treatment option for gMG patients living in Canada."

Gaby Bourbara, Alexion Canada VP & GM said, "Since Alexion brought forward the first complement inhibitor, we've continued to focus on innovating in this category and really understanding the needs of people living with gMG. Today's approval represents a key step forward on behalf of the gMG community in Canada. Ultomiris is the only long-acting C5 inhibitor, and it will benefit a broader range of patients, including those with milder symptoms."

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function, abnormally rapid fatigue of voluntary muscles and severe weakness.^2,3 The diagnosed prevalence of gMG in Canada is estimated at approximately 263 per 1 million population.^4,5

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 haemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The most common side effects of Ultomiris in people with gMG are diarrhea and upper respiratory tract infection.¹ [PM p16A, 17A, 20A, 21A] 

Results from the CHAMPION-MG trial were published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting (available at https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100066).

In addition to the above Canadian approval, Ultomiris is also approved for use in gMG in the EU, Japan and US.

Notes

gMG 

gMG is a rare autoimmune disorder characterised by loss of muscle function and severe muscle weakness.²

The majority of patients with gMG (approximately 85%) have autoantibodies against the postsynaptic acetylcholine receptor (AChR).⁶ This binding activates the complement system, which is essential to the body's defence against infection, causing the immune system to attack the neuromuscular junction.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.^7-9 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.^10,11

CHAMPION-MG

The global Phase III randomized, 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 randomized control period.^1,

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.^1,6

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.^1,6

Ultomiris 

Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor, offers immediate, complete and sustained complement inhibition.⁶ 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 Canada, the US, EU and Japan for the treatment of certain adults with gMG.

Ultomiris is also approved in Canada, 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 Canada, 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 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 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 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.

About AstraZeneca Canada

AstraZeneca is a global, innovation-driven biopharmaceutical business with a focus on the discovery, development, and commercialization of medicines that transform lives. Our core scientific focus is in the areas of Cardiovascular, Renal and Metabolic (CVRM) disease; Oncology; Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, the company employs more than 1,200 people across Canada, including roughly 700 employees at our head office and clinical research hub in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

References

1. ^PrUltomiris^® (ravulizumab) Product Monograph. Alexion Pharma GmbH. January 6, 2023. 

2. Howard, J. Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences. 2018;1412(1):113-128.

3. Muscle.ca. Myasthenia gravis (MG) factsheet. Accessed January 2023 at https://muscle.ca/wp-content/uploads/2019/09/MyastheniaGravis-E.pdf.

4. Carr A, et al. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;10(1):46.

5. Breiner A, et al. Epidemiology of myasthenia gravis in Ontario, Canada. Neuromuscul Disord. 2016;26(1):41-46. 7.

6. Vu, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evid. 2022;1(5).

7. Myasthenia gravis. National organization for rare disorders (NORD). Available at https://rarediseases.org/rare-diseases/myasthenia-gravis/. Accessed January 2023.

8. Howard, J, (2015). Clinical overview of MG. Available at https://myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed January 2023.

9. Sanders, D, et al. The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve. 2020;63(2):209-216.

10. Myasthenia gravis fact sheet. (2020, April 27). National institutes of neurological disorders and stroke. Available at https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed January 2023.

11. Ding, J, et al. Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology. 2020;20(238).

SOURCE Alexion AstraZeneca Rare Disease

Annabel Cowper, [email protected]