New Analysis of MRI Findings Shows Uplizna Reduced the Formation of Subclinical Spinal Cord Lesions in People with NMOSD

Horizon Therapeutics announced the presentation of a new analysis of MRI data from the phase 3 clinical trial of Uplizna showing a reduction in the formation of subclinical (asymptomatic) transverse myelitis lesions in people with NMOSD. This analysis is being presented at the 9th Congress of the European Academy of Neurology (EAN), July 1-4, in Budapest.

Uplizna is the first and only targeted CD19+ B-cell-depleting therapy approved by the FDA, the European Commission and the Brazilian Health Regulatory Agency (ANVISA) for the treatment of NMOSD in adults who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+). The N-MOmentum pivotal trial (NCT02200770) is also the largest phase 3 clinical trial in NMOSD and the only phase 3 trial that collected MRI data, which were also incorporated into its attack adjudication criteria, according to Horizon. Results from this post-hoc analysis demonstrate that Uplizna effectively reduced the formation of subclinical MRI lesions, while also showing an association between subclinical spinal cord lesions and future attacks.

“This analysis offers new insights into the significance of subclinical MRI findings on the spinal cord as a potential signal of future attacks, adding to the growing list of tools available for physicians to better monitor their patients,” Friedemann Paul, study author and Group Leader of the Clinical Neuroimmunology Department of NeuroCure Clinical Research Centre at the Charité, Berlin, said in a company news release. “It is encouraging to see that Uplizna reduced the formation of these lesions. Future studies evaluating subclinical findings will help offer additional clarity on their relationship with disease activity.”

During the trial, MRI imaging was conducted on the spinal cord, optic nerve, and brain/brainstem to quantify the frequency, prognosis and response to treatment with Uplizna of subclinical lesions. This was taken at the time of screening, at the end of the 28-week randomized controlled period (RCP), at the time of any attack and annually during the open-label portion (OLP) of the trial. Of the 134 pivotal trial participants with full neuroaxis MRI and no new NMOSD symptoms at the end of the 28-week RCP, 20 (15%) were found to have asymptomatic MRI lesions on the spinal cord. These lesions were shorter than attack-associated lesions, and importantly were less frequent among those receiving Uplizna.

Subsequent MRI findings showed that the formation of these lesions decreased as treatment with Uplizna continued. Interestingly, these findings showed that subclinical lesions were associated with domain-specific attacks in the following year.

References

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? Accessed April 15, 2021. Guthyjacksonfoundation.org.
   www.guthyjacksonfoundation.org/neuromyelitis-optica-nmo/
3. What We Know About NMO. Accessed Aug. 2, 2022. Sumairafoundation.org.
   https://www.sumairafoundation.org/what-to-know-about-nmo/
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.