Leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein 1(LINGO-1 is a key suppressor of oligodendrocyte differentiation and axonal remyelination and regeneration. This analysis evaluated the potential benefit of opicinumab, a human monoclonal antibody against LINGO-1, vs placebo on exploratory clinical endpoints of patient-reported vision-related functioning and high-contrast visual acuity (HCVA) in RENEW participants with acute optic neuritis (AON).
Participants were randomized to 100 mg/kg opicinumab intravenous or placebo every 4 weeks (6 infusions). Assessments were conducted in the per-protocol (PP) population and included: 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10-item Neuro-Ophthalmic Supplement (NOS-10), and HCVA.
The opicinumab group (n = 33) had worse mean (SD) baseline patient-reported vision-related functioning scores vs placebo (n = 36): NEI-VFQ-25 composite, 75.5 (17.6) vs 79.0 (16.6); NOS-10 composite, 63.6 (19.8) vs 69.8 (21.2), respectively. By Week 24, the placebo and opicinumab groups experienced substantial mean improvements from baseline (NEI-VFQ-25 composite, 15.17 vs 13.51 [difference (95% CI): −1.66 (−5.11 to 1.78)]; NOS-10 composite, 17.40 vs 16.04 [difference (95% CI): −1.35 (−7.38 to 4.67)]). Between-treatment differences in mean change from baseline were not significantly different at any time point. Analysis of covariance–adjusted mean recovery from baseline in HCVA at Week 24 for the affected eyes was 11.8 and 8.7 letters for placebo and opicinumab, respectively (P = 0.202).
Most participants in the RENEW PP population demonstrated substantial recovery from baseline in patient-reported vision-related functioning and HCVA, regardless of treatment and structural damage. Average scores after recovery remained lower than those of published disease-free control groups. These results provide important information on visual function recovery in patients with AON, as measured by NEI-VFQ-25 and NOS-10.
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Department of Value and Access (JP), Biostatistics (YC, LX), and Clinical Development (DC), Biogen, Cambridge, Massachusetts; and Departments of Neurology, Population Health, and Ophthalmology (LB and SG), New York University School of Medicine, New York, New York.
Address correspondence to Jennifer Petrillo, PhD, Global Health Economics and Outcomes Research, Biogen, 225 Binney Street, Cambridge, MA 02142; E-mail: email@example.com
The RENEW study and these analyses were funded by Biogen (Cambridge, MA).
J. Petrillo is an employee of and holds stock/stock options in Biogen. D. Cadavid was an employee of Biogen at the time of these analyses and drafting of the manuscript, and is currently a full-time employee of Fulcrum Therapeutics. Y. Chai and L. Xu were full-time employees of Biogen, Cambridge, MA, at the time of these analyses and drafting of the manuscript, and may hold stock/stock options in Biogen. L. Balcer has received consulting/advisor fees from Biogen and Genzyme. S. Galetta has received consulting fees from Biogen.
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ClinicalTrials.gov identifier: NCT01721161 (BIIB033 In Acute Optic Neuritis (AON); https://clinicaltrials.gov/ct2/show/NCT01721161).