Ultomiris transforms the treatment landscape for AQP4 Ab+ NMOSD patients, with potential to eliminate relapses and improve outcomes
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
Gaby Bourbara, General Manager of
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
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 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
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 (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
Ultomiris is also approved in the US, EU and
Additionally, Ultomiris is approved in the US, EU and
Further, Ultomiris is approved in the EU and
As part of a broad development programme, Ultomiris is being assessed for the treatment of additional haematology and neurology indications.
Alexion, AstraZeneca Rare Disease, is the group within
References
- Ultomiris Draft Product Monograph, Alexion Pharma GmbH.
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- Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica. Neurologist. 2007;13(1):2-11.
- 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.
- Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10(1):55-66.
- 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. - 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.
- 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 . - Cossburn, M., et al. (2012). The Prevalence of Neuromyelitis Optica in South East Wales. Eur J Neurol., 19(4): 655-659.
- Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10(9):493.
- Takata K, Matsuzaki T, Tajika Y. Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem. 2004;39(1):1-83.
- 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 . National Institute of Neurological Disorders and Stroke . Neuromyelitis Optica.April 2023 . Available online. AccessedOctober 2023 .- 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.
- Jarius, S., Wildemann, B. (2013). The History of Neuromyelitis Optica. J Neuroinflammation 10, 797.
- 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.
- ClinicalTrials.gov. An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD. NCT Identifier: NCT04201262. Available online. Accessed
May 2023 .
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