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Analysis demonstrates inebilizumab-cdon reduces severity of attacks linked with neuromyelitis optica spectrum disorder


According to data presented by Horizon Therapeutics at the North American Neuro-Ophthalmology Society annual meeting held this week in Austin, Texas, Uplizna treatment is linked to fewer severe attacks and reduced levels of key disease-related biomarkers versus placebo.

Horizon Therapeutics on Wednesday announced results from a new analysis showing treatment with inebilizumab-cdon (Uplizna) effectively reduced the severity of attacks in people with NMOSD.

The data are being presented at the 48th annual meeting of the North American Neuro-Ophthalmology Society (NANOS 2022), being held February 12-17 in Austin, Texas.

According to the company, inebilizumab-cdon is the first and only B-cell-depleting agent approved by the FDA for the treatment of NMOSD in adults who are anti-aquaporin-4 (AQP4) antibody positive.

Treatment of NMOSD aims to reduce acute attacks associated with the disease, which can cause irreversible damage to the optic nerve, spinal cord, brain and brain stem.

During the 28-week randomly assigned, controlled period (RCP) of the N-MOmentum Phase 2/3 pivotal trial, 89% of 161 patients in the inebilizumab-cdon treatment group remained attack-free compared to 58% of 52 patients in the placebo group.

The company noted in a news release that a new post hoc analysis of this data was conducted to understand the effect of inebilizumab-cdon on the severity of attacks in the 11% of people in the clinical trial who were not attack-free after being treated with inebilizumab-cdon. Attacks were graded as major or minor based on changes in neurological function according to a modified Opticospinal Impairment Scale (OSIS).

The analysis also evaluated the relationship between the severity of these attacks and biomarkers of disease activity, such as serum glial fibrillary acidic protein (sGFAP) and serum neurofilament (sNfL).

“Acute attacks in NMOSD can lead to irreversible consequences and permanent disability in patients, making targeted treatments important to limit disease activity and its severity in patients,” said Jeffrey Bennett, MD, PhD, University of Colorado and study author. “This analysis illustrates the clear clinical impact of Uplizna to reduce the debilitating effects of disease while contributing to our understanding of the link between serum biomarkers and severity of attacks.”

Key analysis findings:

  • Of the 18 total attacks that occurred in the inebilizumab-cdon treatment group during the RCP, 12 (67%) were minor and six (33%) were major, compared to 12 (55%) minor attacks and 10 (45%) major attacks among the 22 attacks occurring in the placebo group.
  • Levels of the sGFAP biomarker were significantly higher during major attacks versus minor attacks overall (p = 0.023) and trended higher for optic neuritis (ON) specific attacks (n = 20, p = 0.06). Concentration levels of the biomarker increased significantly from baseline at the time of attacks in those receiving placebo but not in those treated with inebilizumab-cdon (p = 0.31).
  • SNfL levels were higher for major versus minor attacks overall (p = 0.032), though the levels did not correlate with the severity of ON attacks. In participants that had attacks during the RCP, rates of this marker were higher among placebo versus inebilizumab-cdon -treated participants at Week 26 (p = 0.03).

“While the Uplizna clinical trial demonstrated that a majority of patients were attack-free after being treated, it also offered an increased understanding of how UPLIZNA impacted the severity of the attacks that occurred,” said Kristina Patterson, MD, PhD, medical director, neuroimmunology, Horizon. “This is an important consideration for physicians as they evaluate treatment options for their patients, as severe attacks can have debilitating consequences.”

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. It is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.1,2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.4

Anti-AQP4 autoantibodies are produced by plasmablasts and plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.5 Depletion of these CD19+ B cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8,9NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10,11

inebilizumab-cdon (Uplizna, Horizon Therapeutics) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.


  1. 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.
  2. What is NMO? Guthyjacksonfoundation.orgwww.guthyjacksonfoundation.org/neuromyelitis-optica-nmo/Accessed April 15, 2021.
  3. Layman’s Guide to NMO. Sumairafoundation.orghttps://www.sumairafoundation.org/laymans-guide-to-nmo/ Accessed April 25, 2021.
  4. 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.
  5. Chihara N, et al. Interleukin 6 signaling promotes anti-aquaporin-4 autoantibody production from plasmablasts in neuromyelitis optica. PNAS. 2011;108(9):3701-3706.
  6. Duan T, Smith AJ, Verkamn AS. Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody dependent cellular cytotoxicity. Acta Neuropathologica Comm. 2019;7(112).
  7. Beekman J, et al. Neuromyelitis optica spectrum disorder: patient experience and quality of life. Neural Neuroimmunol Neuroinflamm. 2019;6(4):e580.
  8. Kimbrough DJ, et al. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord. 2012;1(4):180-187.
  9. 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.
  10. Wingerchuk DM. Neuromyelitis optica: effect of gender. J Neurol Sci. 2009;286(1-2):18-23.
  11. Flanagan EP, et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. 2016;79(5):775-783.
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