Horizon Therapeutics Announces New Analysis of MRI Findings Show UPLIZNA Reduced Formation of Asymptomatic Optic Nerve Lesions in People With NMOSD

Horizon Therapeutics plc (Nasdaq: NASDAQ:HZNP) today announced the presentation of new MRI imaging data from the Phase 3 clinical trial showing UPLIZNA reduced the formation of subclinical (asymptomatic) optic nerve lesions in people with NMOSD. These findings are being presented during the 49th annual meeting of the North American Neuro-Ophthalmology Society (NANOS) March 11-16, 2023, in Orlando, Florida.

UPLIZNA is the first and only B-cell depleting monotherapy approved by the U.S. Food and Drug Administration, 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 only Phase 3 clinical trial in NMOSD that collected MRI data and integrated MRI into its attack adjudication criteria. Results from the study demonstrated the significant effect of UPLIZNA in reducing the risk of NMOSD-associated attacks. This new post-hoc analysis based on MRI imaging provides a deeper understanding of the treatment effect on subclinical lesions.

“Data presented at the NANOS meeting show that gadolinium enhancement events of the optic nerve may occur in NMO patients without causing optic neuritis,” said Bruce Cree, M.D., Ph.D., MAS, study author and professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences. “Although these subclinical optic nerve findings were smaller than those associated with optic neuritis attacks and were not predictive of future attacks, that the enhancement events occur shows there is a greater degree of complexity to attack pathogenesis in NMO than was previously appreciated. How these subclinical enhancement events contribute to the overall disease burden in NMO remains to be determined. Nevertheless, it is encouraging to see that repeated use of UPLIZNA decreased the rate of these subclinical optic nerve enhancements events over time.”

During the trial, MRI imaging was conducted on the spinal cord, optic nerve and brain/brainstem to quantify the frequency, prognosis and treatment response to UPLIZNA of subclinical lesions. This imaging was captured at the time of screening and at the end of the randomized controlled period (RCP), at the time of any attack and annually during the open label portion (OLP) of the trial.

The MRI findings showed that a high proportion of participants experienced subclinical optic nerve findings without new symptoms at the end of the RCP. These were shorter (median length 6 mm) than in those with an optic nerve attack (15 mm, p<0.001) and were not found to be associated with future attacks. Importantly, while the total subclinical findings in the optic nerve were not reduced during the RCP, the number of clinical optic neuritis attacks was significantly reduced during this time period. Moreover, the formation of these subclinical findings was reduced with repeated UPLIZNA treatment over the course of the OLP.

“The use of MRI in the Phase 3 clinical trial has enabled us to better quantify not only the most visible effects of NMOSD attacks, but also changes in disease patterns at the subclinical level that may compound over time,” said Kristina Patterson, M.D., PhD, medical director, neuroimmunology, Horizon. “These data help deepen our understanding of the real biological impact of this medicine not just on the attacks, but also on asymptomatic activity, further reinforcing the robust clinical profile of UPLIZNA in controlling the effects of this challenging disease and supporting long-term patient care.”