Health Canada approves Ultomiris for adults with neuromyelitis optica spectrum disorder (NMOSD)

Ultomiris transforms the treatment landscape for AQP4 Ab+ NMOSD patients, with potential to eliminate relapses and improve outcomes

MISSISSAUGA, ON, Nov. 1, 2023 /CNW/ - Ultomiris (ravulizumab) has been approved by Health Canada as the first and only long-acting C5 complement inhibitor for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD).¹

This approval comes following the CHAMPION-NMOSD Phase III trial, which was published online in the Annals of Neurology and selected as an abstract of distinction at the 2023 American Academy of Neurology Annual Meeting.² In the trial, Ultomiris was compared to an external placebo arm from the pivotal Soliris PREVENT clinical trial.

Ultomiris met the primary endpoint of time to first on-trial relapse as confirmed by an independent adjudication committee. Zero adjudicated relapses were observed among Ultomiris patients with a median treatment duration of 73 weeks.

NMOSD is a rare autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves.^3-5 Most people living with NMOSD experience unpredictable relapses, characterised by a new onset of neurologic symptoms or worsening of existing neurologic symptoms, which tend to be severe and recurrent and may result in permanent disability.^6-8

Galina Vorobeychik, MD, Clinical Associate Professor (Neurology) at the University of British Columbia and Director at the Fraser Health Multiple Sclerosis Clinic at Burnaby Hospital, said: "NMOSD is a rare disease that has significant impact on patients' lives. I am hopeful that the approval of this new therapy will improve the future outlook of those living with NMOSD in Canada. The huge benefits are that the amount of ravulizumab is determined by a patient's weight and infused once every eight weeks which allows patients to travel and maintain their regular life between infusions."

Sumaira Ahmed, an NMOSD patient herself and the founder and Executive Director of The Sumaira Foundation, said: "The approval of ravulizumab for NMOSD represents a therapy option that works via the immune system complement pathway, with a much less frequent infusion dosing schedule of once every eight weeks. This represents a real innovation and improvement for our patient community, greatly simplifying work/life balance, travel plans, and the daily lived experience for NMOSD patients. Patients can vary in their response to medicines, so having a wider range of therapy options to choose from is very important to patients and clinicians in successfully managing this rare but serious condition."

Gaby Bourbara, General Manager of Alexion Canada, said: "We are thrilled that Canadians living with NMOSD now have a new therapy option to help them manage this challenging disease. We look forward to partnering with key stakeholders and payer partners across the country to ensure it is reimbursed. It is critical that progress is made on the implementation of Canada's rare disease strategy and that patients have accelerated access to innovative therapies they need to live healthier lives."

Overall, the safety and tolerability of Ultomiris in the CHAMPION-NMOSD trial were consistent with previous clinical studies and real-world use, and no new safety signals were observed. The most common adverse events (AEs) were COVID-19, headache, back pain, arthralgia and urinary tract infection. All cases of COVID-19 were non-serious and considered to be unrelated to Ultomiris.²

Ultomiris is currently approved for the treatment of certain adults with NMOSD in the European Union (EU), Japan and other countries. 

Notes

NMOSD

NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.^3,4 Specific serum anti-aquaporin-4 antibodies (AQP4-ab) are pathogenic and identified in most patients with NMOSD and this means they produce antibodies that bind to AQP4.⁹ This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body's defence against infection, to destroy cells in the optic nerve, spinal cord and brain.^3,10,11

It has been found that NMOSD is more common in women and the average age of onset is early 30s to mid-40s.¹³ People with NMOSD may experience optic neuritis, which causes pain in the eye and vision loss, transverse myelitis which causes weakness or paralysis of arms and legs, numbness, loss of bladder and bowel control, severe nausea and vomiting and subsequent hiccups from involvement of a part of the brain that controls vomiting.¹⁴ Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death.^6-8 NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.^15-17

CHAMPION-NMOSD

CHAMPION-NMOSD is a global Phase III, open-label, multi-centre trial evaluating the safety and efficacy of Ultomiris in adults with NMOSD. The trial enrolled 58 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least one attack or relapse in the twelve months prior to the screening visit, an Expanded Disability Status Scale Score of 7 or less and body weight of at least 40 kilograms at trial entry. Participants could stay on stable supportive immunosuppressive therapy for the duration of the trial.¹⁸

Due to the potential long-term functional impact of NMOSD relapses and available effective treatment options, a direct placebo comparator arm was precluded for ethical reasons. The active treatment was compared to an external placebo arm from the pivotal Soliris PREVENT clinical trial.

Over a median treatment duration of 73 weeks, all enrolled patients received a single weight-based loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint was time to first on-trial relapse, as confirmed by an independent adjudication committee. The end of the primary treatment period could have occurred either when all patients completed or discontinued prior to the Week 26 visit and two or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the Week 50 visit if fewer than two adjudicated relapses were observed. In the trial, there were zero adjudicated relapses, so the end of the primary treatment period occurred when the last enrolled participant completed the 50-week visit.

Patients who completed the primary treatment period were eligible to continue into a long-term extension period, which is ongoing.

Ultomiris

Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor, provides 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 generalised myasthenia gravis.

Ultomiris is also approved in the US, EU and Japan for the treatment of certain adults with paroxysmal nocturnal haemoglobinuria (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 atypical haemolytic uraemic syndrome to inhibit complement-mediated thrombotic microangiopathy.

Further, Ultomiris is approved in the EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

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 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. Please visit https://alexion.com/worldwide/canada.

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 www.astrazeneca.ca and follow the Company on X @AstraZenecaCA.

References

1. Ultomiris Draft Product Monograph, Alexion Pharma GmbH. October 30, 2023.
2. Pittock et al. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol. 2023 Jun;93(6):1053-1068. Available online. Accessed October 2023.
3. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805-815.
4. Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica. Neurologist. 2007;13(1):2-11.
5. Hamid SHM, Whittam D, Mutch K et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088-2094.
6. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10(1):55-66.
7. Kitley J, Leite MI, Nakashima I, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(6):1834-1849.
8. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflamm. 2012;9:14.
9. Wang L, Du L, Li Q, Li F, Wang B, Zhao Y, Meng Q, Li W, Pan J, Xia J, Wu S, Yang J, Li H, Ma J, ZhangBao J, Huang W, Chang X, Tan H, Yu J, Zhou L, Lu C, Wang M, Dong Q, Lu J, Zhao C and Quan C (2022) Neuromyelitis Optica Spectrum Disorder With Anti-Aquaporin-4 Antibody: Outcome Prediction Models. Front. Immunol. 13:873576. doi: Available online. Accessed October 2023.
10. Cossburn, M., et al. (2012). The Prevalence of Neuromyelitis Optica in South East Wales. Eur J Neurol., 19(4): 655-659.
11. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10(9):493.
12. Takata K, Matsuzaki T, Tajika Y. Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem. 2004;39(1):1-83.
13. Pandit L, Asgari N, Apiwattanakul M, Palace J, Paul F, Leite MI, Kleiter I, Chitnis T; GJCF International Clinical Consortium & Biorepository for Neuromyelitis Optica. Demographic and clinical features of neuromyelitis optica: A review. Mult Scler. 2015 Jun;21(7):845-53. doi: 10.1177/1352458515572406. Epub 2015 Apr 28. PMID: 25921037; PMCID: PMC4463026. Available online. Accessed October 2023.
14. National Institute of Neurological Disorders and Stroke. Neuromyelitis Optica. April 2023. Available online. Accessed October 2023.
15. Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol. 2013;254(1-2):178-182.
16. Jarius, S., Wildemann, B. (2013). The History of Neuromyelitis Optica. J Neuroinflammation 10, 797.
17. Mealy, M. A., et al. (2019). Assessment of Patients with Neuromyelitis Optica Spectrum Disorder Using the EQ-5D. International journal of MS care, 21(3), 129–134.
18. ClinicalTrials.gov. An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD. NCT Identifier: NCT04201262. Available online. Accessed May 2023.

SOURCE Alexion AstraZeneca Rare Disease

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