Horizon Therapeutics plc Receives European Commission (EC) Approval of UPLIZNA® (inebilizumab) for the Treatment of Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD)
Horizon Therapeutics has received European Commission approval for UPLIZNA (inebilizumab) as monotherapy for adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are AQP4-IgG+. This medication, the first targeted CD19+ B-cell-depleting therapy approved in the EU for NMOSD, showed significant efficacy in the pivotal N-MOmentum trial, where 87.6% of treated patients remained attack-free for 28 weeks. With approximately 7,300 NMOSD patients in Europe, the approval provides new hope for effective treatment amidst the severe impacts of this disease.
- European Commission approved UPLIZNA as the first targeted CD19+ B-cell-depleting monotherapy for NMOSD.
- In the N-MOmentum trial, 87.6% of AQP4-IgG+ patients were attack-free for 28 weeks.
- UPLIZNA has potential to significantly reduce attack frequency and improve quality of life for approximately 7,300 NMOSD patients in Europe.
- There are potential risks related to the commercialization and patient accessibility of UPLIZNA across different EU countries.
- Market competition and uncertainties surrounding pricing strategies for UPLIZNA in the EU.
-- NMOSD is a devastating autoimmune disease of severe and recurrent central nervous system attacks which can result in blindness, paralysis and death --
-- UPLIZNA is indicated as monotherapy for treatment of adult patients with NMOSD who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+), which represents
-- EC approval was supported by results from N-MOmemtum, the largest pivotal trial ever conducted in NMOSD, which showed
-- UPLIZNA is the EU’s first and only targeted CD19+ B-cell-depleting monotherapy proven to reduce attacks in adult AQP4-IgG+ NMOSD patients --
“NMOSD is a devastating disease with unpredictable attacks, cumulative and often irreversible damage and potential loss of vision and motor function, causing profound uncertainty for patients,” said
People impacted by NMOSD live with unpredictable attacks;
In the N-MOmentum pivotal clinical trial (2014-000253-36), the largest NMOSD trial to date, UPLIZNA demonstrated a significant reduction in the risk of an NMOSD attack with only two infusions per year, following the initial loading doses. Additionally,
“We have made great strides in understanding the pathogenesis of NMOSD and in identifying new, effective therapies for its treatment, such as UPLIZNA, which can be transformative for patients in
Globally, the prevalence of NMOSD is approximately 0.5–4/100,000 people,6,7 and women are nine times more likely to be impacted than men.8 Consequences of this disease extend beyond the clinical impact, including physical, functional and psychological impact on patients’ quality of life.9,10 In
UPLIZNA was approved by the
About Neuromyelitis Optica Spectrum Disorder (NMOSD)
NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.13,14 Approximately
Anti-AQP4 autoantibodies are produced by plasmablasts and some plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19. Depletion of these CD19+ B-cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage.
About the N-MOmentum Clinical Program
N-MOmentum was a multicentre, double-blind, randomised placebo-controlled Phase 2/3 clinical trial that was conducted in 25 countries. A total of 230 participants were enrolled: 213 were AQP4-IgG seropositive, and 17 were AQP4 IgG seronegative. Participants were randomly assigned at a ratio of 3 (on treatment) to 1 (on placebo). The study consisted of a 28-week randomised-controlled period (RCP), followed by an optional open-label period (OLP) of at least two years. The OLP lasted approximately four years, producing long-term data for a subset of patients (n=75 AQP4+ patients).3,4
The trial Primary Endpoint was:
- Time to onset of NMOSD relapse on or before Day 197.
The trial key Secondary Endpoints were:
- Percentage of patients with worsening in Expanded Disability Severity Scale (EDSS) from baseline to the last visit of the RCP: EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time.
- Change from baseline in Low-Contrast Visual Acuity Binocular (LCVAB) Score to the last visit of the RCP: The low-contrast visual acuity test is used to determine the number of letters that can be read on a standardised low-contrast Landolt C Broken Rings Chart held at a distance of three metres. The binocular score is the number of letters read correctly on an eye chart using both eyes simultaneously.
- Number of active Magnetic Resonance Imaging (MRI) lesions during the RCP: The number of new lesions were measured by MRI of the brain, optic nerve and spinal cord.
- Number of NMOSD-related in-patient hospitalisations during the RCP: Participants with relapsing NMOSD have recurrent attacks that can be severe and result in blindness, paralysis and even death and, consequently, such attacks frequently result in in-patient hospitalisations (defined as a stay in hospital that goes beyond midnight of the first day of admission).
In the N-MOmentum trial, UPLIZNA had a favourable safety profile. The most common adverse reactions (at least
During the trial, B-cell counts were determined using high-resolution flow cytometry (captured as cells/µL). Disease activity was measured using annualised attack rates (AAR) and the number of new or enlarging T2 lesions in the brain or spine.
Due to demonstrated superior efficacy achieved in the UPLIZNA treatment arm versus placebo, the N-MOmentum trial was stopped early on the recommendation of the Independent Data Monitoring Committee.
About Horizon
Horizon is focused on the discovery, development and commercialisation of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to the timing of a potential commercial launch of UPLIZNA in the EU, the potential benefits of UPLIZNA to patients in EU and Horizon’s global expansion plans. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include the actual timing of launching UPLIZNA in the EU, whether UPLIZNA is successfully commercialised in the EU, and those risks detailed from time-to-time under the caption "Risk Factors" and elsewhere in Horizon’s filings and reports with the
References
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Rensel M, Zabeti A, Mealy M et al. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4–immunoglobulin G–seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial.
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Cree BA, Bennett JL et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-Momentum): a double-blind, randomised placebo-controlled phase 2/3 trial.
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Contetti EC, Correale J. Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies.
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Mori M, et al. Worldwide prevalence of neuromyelitis optica spectrum disorders.
Journal of Neurology , Neurosurgery & Psychiatry. 2018;89:555-556. - Wingerchuk DM. Neuromyelitis optica: effect of gender. J. Neurol Sci. 2009;286(1-2):18-23
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Kazuo Fujihara , et al, Patient-reported burden of symptoms in neuromyelitis optica: A secondary analysis on pain and quality of life,Journal of the Neurological Sciences , Volume 428, 2021, 117546, ISSN 0022-510X, https://doi.org/10.1016/j.jns.2021.117546 - Beekman J, et al. Neuromyelitis optica spectrum disorder: Patient experience and quality of life. Neurol Neuroimmunol Neuroinflamm. 2019;6(4):e580. Published 2019 Jun 20. doi:10.1212/NXI.0000000000000580
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- Ajmera MR, Boscoe A, Mauskopf J, Candrilli SD, Levy M. Evaluation of comorbidities and health care resource use among patients with highly active neuromyelitis optica. J Neurol Sci. 2018; 384:96-103.
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What is NMO? Guthyjacksonfoundation.org. www.guthyjacksonfoundation.org/neuromyelitis-optica-nmo/ Accessed
March 15, 2022 . - Liu Y, et al. A tract-based diffusion study of cerebral white matter in neuromyelitis optica reveals widespread pathological alterations. Mult Scler. 2011;18(7):1013-1021.
- Duan T, Smith AJ, Verkamn AS. Complement-independent bystander injury in AQP4-IgG seropositive cytotoxicity. Acta Neuropathologica Comm. 2019;7(112).
- Kimbrough DJ, et al. Treatment of neuromyelitis optica: review recommendations. Mult Scler Relat Disord. 2012;1(4):180-187.
- Baranello RJ, Avasarala JR. Neuromyelitis optica spectrum disorders with and without aquaporin 4 antibody: Characterization, differential diagnosis, and recent advances. J Neuro Ther. 2015;1(1):9-14.
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