New Analysis From N-MOmentum Clinical Trial of Uplinza Demonstrate Process that Could Improve Clinical Care Process for NMOSD

Horizon Therapeutics announced the publication of a new analysis from the N-MOmentum clinical trial of Uplinza demonstrating the utility of an adjudication process that could improve clinical care decision-making in neuromyelitis optica spectrum disorder (NMOSD) through more accurate and consistent assessment of disease-related attacks. These findings are published in the Multiple Sclerosis Journal.

NMOSD is characterized by recurrent disabling attacks, which often lead to permanent disability. Properly defining NMOSD attacks is essential to inform treatment decisions, yet there are no universally accepted criteria for accurate and objective diagnosis of NMOSD attacks, according to Horizon.

The N-MOmentum pivotal trial, which demonstrated Uplinza reduced the risk of attacks associated with the disease, introduced a new approach for attack analysis. Attacks were evaluated by an adjudication committee (AC, comprised of two neurologists and one neuro-ophthalmologist). The approach was revised based on guidance from the FDA. The process evaluated 18 predefined criteria (covering optic neuritis, myelitis and brain/brainstem domains). Domain-specific MRI review was performed in scenarios where the clinical findings were indeterminant. This analysis assessed the accuracy of the attack adjudication criteria against a retrospective review of MRI (for those attacks where MRI was not reviewed) as well as assess the biomarker serum glial fibrillary acidic protein (sGFAP, a structural filament protein that is released following injury of the central nervous system).

“The adjudication process provided an accurate, reliable understanding of the nature of NMOSD attacks, with MRI correlates and biomarker elevations found in the vast majority of adjudicated attacks,” Brian Weinshenker, MD, study author and professor of neurology, University of Virginia School of Medicine, said in a company news release. “Conversely, events reported as attacks by investigators that were not adjudicated by the AC were usually not accompanied by objective corroboration of attacks by MRI or biomarker elevation. Without accurate criteria, attacks may go undetected or symptoms not indicative of true attacks may be misclassified, leading to potentially erroneous interpretation of study results. The process outlined in this study may serve as a useful benchmark to inform future attack evaluations, while also helping clinicians contextualize the efficacy of Uplinza and other NMOSD treatments.”

Of the 230 participants in the trial, 64 participant-reported neurological events occurred; 51 of these (80%) were deemed attacks by the trial investigators and of those, 43 (84%) were independently confirmed by the AC. The use of detailed, predefined criteria enabled reliable and reproducible determinations, as only 16% of investigator-determined attacks were rejected following AC review and no investigator-rejected attack decisions were reversed by the AC.

MRI and sGFAP biomarker findings provided additional specificity in the attack adjudication process. New domain-specific lesions were found in 90% of adjudicated attacks for which MRI data were available, and use of MRI allowed for confirmation of 33% of adjudicated attacks for which clinical findings were inconclusive. Further, increased concentrations of sGFAP (>2-fold mean change from baseline) were observed in more than half (56%) of adjudicated attacks, reinforcing the potential role of sGFAP in NMOSD attacks and supporting the use of sGFAP measurements in clinical care. Importantly, sGFAP elevations were notably less common in Uplinza-treated participants than those receiving placebo, consistent with previous findings showing the effectiveness of Uplinza in reducing sGFAP levels.

“Together with well-defined review criteria and biomarker analysis, this robust adjudication process could serve as the basis for consistent attack evaluations in future studies and real-world care,” said Kristina Patterson, MD, PhD, senior medical director, neuroimmunology medical affairs, Horizon. “Importantly, the accurate picture of disease-related attack events seen in this analysis further reinforces the efficacy of Uplinza in reducing these attacks and improving outcomes for people with NMOSD.”