A subset group of inebilizumab-treated patients who did not have adjudicated attacks displayed more than a 2-fold increase in serum CSF glial fibrillary acidic protein from baseline, implying GFAP may serve as a biomarker.
Bruce Cree, MD, PhD, MAS
Data presented at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting on the N-MOmentum trial (NCT02200770) revealed that patients with neuromyelitis optica spectrum disorder (NMOSD) have increased levels of cerebrospinal fluid glial fibrillary acidic protein (GFAP), indicating that the protein may serve as a biomarker of attack risk and disease activity and severity.1
Bruce Cree, MD, PhD, MAS, senior author, and neurologist, UCSF Multiple Sclerosis Center, and colleagues found that study participants with elevated serum GFAP (sGFAP) levels were 2.9 times more likely to experience an adjudicated NMOSD attack than those with lower baseline sGFAP during the 28-week randomized controlled period (RCP; P = .002). Elevated sGFAP, defined as >3 standard deviations (SDs) above the mean control (>171 pg/mL), was observed in 61 of 215 (29%) study participants with NMOSD at baseline.
N-MOmentum, a randomized, placebo-controlled, double-masked trial of inebilizumab (Viela Bio), measured sGFAP in 1260 serial and attack-related samples collected from study participants (n = 220) and in healthy controls (n = 25). sGFAP levels increased significantly within 1 week of an NMOSD attack in placebo-treated participants (median fold change, 20.2 [interquartile range (IQR), 4.4—98.3]; n = 17 attacks; P = .001) but did not increase significantly during attacks in inebilizumab-treated patients (mean fold change, 1.1 [IQR, 0.75—24.6]; n = 20 attacks; P >.05) during the RCP.
Cree and coauthors noted that 14 (2.7%) samples from 12 patients among a cohort of 514 samples drawn from inebilizumab-treated patients during the RCP who did not have adjudicated attacks had ≥2-fold increase in sGFAP from baseline, compared to 9 of 116 samples (8%) from 6 placebo-treated patients (odds ratio [OR], 3.0; P = .023).
Of the 143 participants who did not have an adjudicated NMOSD attack during the RCP, 19 of 117 (16%) inebulizumab-treated patients and 9 of 26 (35%) placebo-treated patients had elevated sGFAP levels at the end of RCP, respectively.
The study population showed median sGFAP levels were elevated in patients with NMOSD compared with controls (NMOSD: median, 128.3 [IQR, 92.5—182.1]; controls: median 73.3 [IQR, 52.1–108.7]). The study objective of N-MOmentum was to investigate the relationship between prospectively sampled sGFAP levels and disease activity, including NMOSD attacks, in study participants.
Researchers used time to Adjudication Committee (AC)-Determined NMOSD attack during RCP from baseline to Day 197 as the primary outcome of the study. Other top-line secondary end points documented were the percentage of participants with worsening in Expanded Disability Severity Scale (EDSS) score from baseline to last visit of RCP and change from baseline in low-contrast visual acuity binocular score to the last visit of RCP.
Inebilizumab, the study drug, was previously granted a breakthrough therapy designation from the FDA for the treatment of NMOSD in April 2019.2 In August of that year, Viela Bio announced the FDA had accepted its Biologics License Application (BLA) for the investigational anti-CD19 monoclonal antibody. Both decisions were made based on results from N-MOmentum, which showed a 77% reduction in risk of developing an NMOSD attack when treated with inebilizumab compared to placebo in AQP4-IgG seropositive patients after 28 weeks of treatment.3
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1. Hartung HP, Aktas O, Smith MA, et al. Serum glial fibrillary acidic protein is elevated in a subset of neurmyelitis optica patients and associated with increased risk of attacks. Int J MS Care. 2020;22(2 Suppl). DAM04.
2. Viela Bio Receives U.S. FDA Breakthrough Therapy Designation for Inebilizumab for Treatment of Neuromyelitis Optica Spectrum Disorder [press release]. Gaithersburg, MD: Veila Bio; Published April 18, 2019. Accessed May 28, 2020. businesswire.com/news/home/20190418005188/en/Viela-Bio-Receives-U.S.-FDA-Breakthrough-Therapy.
3. Viela Bio announces US FDA accepts for review Inebilizumab biologics license application for neuromyelitis optica spectrum disorder [news release]. Gaithersburg, MD: Viela Bio. Published August 27, 2019. Accessed May 28, 2020. biospace.com/article/releases/viela-bio-announces-u-s-fda-accepts-for-review-inebilizumab-biologics-license-application-for-neuromyelitis-optica-spectrum-disorder