New Data Published from Phase 3 N-MOmentum Trial of Horizon's Uplinza
Horizon Therapeutics announced the publication of new data from the Phase 3 N-MOmentum pivotal trial of Uplinza. The data offer insights on serum biomarkers that signal acute attacks and disability worsening associated with NMOSD and illustrate the role of Uplinza in reducing these biomarker levels, potentially reducing the frequency and severity of these attacks, according to a company news release.
The results of this analysis are published in The Journal of Neurology, Neurosurgery and Psychiatry.
NMOSD is most notably associated with acute attacks, which can cause irreversible damage to the optic nerve, spinal cord, brain and brain stem. Disease management goals are focused on prevention of attacks, as well as understanding and tracking biomarkers that could signal these attacks. The N-MOmentum pivotal trial of Uplinza, which demonstrated the effects of the treatment in reducing the attacks associated with NMOSD, included analyses of biomarkers linked to disease activity and neuronal injury: serum neurofilament light chain (sNfL, a structural protein increasingly recognized as a signal of neuronal injury), serum glial fibrillary acidic protein (sGFAP, a marker previously found to correlate with NMOSD attacks), ubiquitin C-terminal hydrolase L1 (sUCHL1), and tau (sTau).
The trial identified important biomarker trends associated with NMOSD attacks. Throughout the 28-week randomized controlled trial period (RCP) and the 2-year open-label follow-up period, the concentration of all four biomarkers increased during NMOSD attacks, and in the days leading up to attacks. Of the four biomarkers evaluated in the trial, sNfL measured at the time of attack was the strongest predictor of worsening disability during and after attacks (as measured by Expanded Disability Status Scale, or EDSS). The strong link suggests that higher sNfL levels may be associated with more severe attacks and increased risk of residual disability. However, only levels of sGFAP were determined to be predictive of future attacks, building upon prior research studying that biomarker in particular.
“This analysis provides valuable insights into how we can improve care for people with NMOSD by integrating easily accessible serum biomarker assessments into treatment decision-making,” Orhan Aktas, MD, Professor at the Department of Neurology, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany, said in a company news release. “Conducting assessments of the sNfL biomarker during an attack can inform clinicians about the attack severity and the likelihood of residual disability in the patient, and therefore may guide therapeutic interventions to help preserve their long-term outcomes. Combination with other select serum biomarkers such as sGFAP may further increase prediction of clinical activity and, thus, prognosis in this devastating disorder.”
Biomarker changes among Uplinza-treated participants in the trial reinforced the effects of this medicine, according to Horizon. Compared with placebo, Uplinza was shown to hinder biomarker elevation during attacks while reducing biomarker levels over time in the absence of attacks. Participants treated with Uplinza had significantly lower levels of sNfL at the end of the RCP compared to placebo (22% vs. 45% of participants with sNfL levels above 16 mg/mL, respectively), and numerically lower levels of the other three biomarkers. Among patients who did experience attacks, those treated with Uplinza had lower biomarker levels during attacks versus those who received placebo, reflecting potentially less severe events, and sGFAP levels were significantly lower with Uplinza among those who did not experience attacks versus placebo.
“These findings support the strong clinical profile of Uplinza as a leading therapeutic option for NMOSD, with compelling evidence of its direct effects on critical biomarkers that signal disease activity and disability,” said Kristina Patterson, MD, PhD, senior medical director, neuroimmunology medical affairs, Horizon. “The availability of these data in a rare and challenging disease like NMOSD can inform disease management strategies and contribute to improved outcomes for this population over time.”