— Analysis in The Journal of Neurology, Neurosurgery and Psychiatry demonstrate the direct effect of UPLIZNA on levels of sNFL and sGFAP, two key biomarkers strongly associated with NMOSD attacks and disability —
Horizon Therapeutics plc (NASDAQ:HZNP) today announced the publication of new data from the Phase 3 N-MOmentum pivotal trial of UPLIZNA, which offer insights on serum biomarkers that signal acute attacks and disability worsening associated with NMOSD and illustrate the role of UPLIZNA in reducing these biomarker levels, potentially reducing the frequency and severity of these attacks. 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 UPLIZNA, 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 two-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,” said Orhan Aktas, M.D., Professor at the Department of Neurology, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany. “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.”
Importantly, biomarker changes among UPLIZNA-treated participants in the trial reinforced the effects of this medicine. Compared with placebo, UPLIZNA was shown to hinder biomarker elevation during attacks while reducing biomarker levels over time in the absence of attacks. Participants treated with UPLIZNA 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 UPLIZNA had lower biomarker levels during attacks versus those who received placebo, reflecting potentially less severe events, and sGFAP levels were significantly lower with UPLIZNA among those who did not experience attacks versus placebo.
“These findings support the strong clinical profile of UPLIZNA 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, M.D., Ph.D., 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.”
About Neuromyelitis Optica Spectrum Disorder (NMOSD)
NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD 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.8-9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10-11
