Ozanimod (RPC1063) Reduces Plasma Levels of Neurofilament Light Chain (NfL) in Patients With Relapsing Multiple Sclerosis (RMS): Results From RADIANCE Part A, a Randomized, Placebo-Controlled, Phase 2 Study (P3.395)

Objective: To evaluate plasma NfL levels in patients with RMS participating in RADIANCE Part A. Background: Ozanimod, a once-daily, oral immunomodulator that selectively targets sphingosine 1-phosphate receptor 1 (S1P R1 ) and 5 (S1P R5 ), has shown therapeutic benefit in clinical studies of RMS. Modulation of S1P R1 on lymphocytes may disrupt the inflammatory cascade of MS. NfL, which is released into cerebrospinal fluid and serum/plasma following axonal/neuronal injury, may serve as a putative biomarker for neurologic damage. Design/Methods: In RADIANCE Part A (NCT01628393), patients with RMS were randomized (1:1:1) to once-daily oral ozanimod 0.5 mg (n=87) or 1.0 mg (n=83) or placebo (n=88) for 24 weeks. The primary endpoint was mean cumulative number of gadolinium-enhancing lesions from weeks 12–24. Mean cumulative number of new/enlarging T2 lesions from weeks 12–24 was a secondary endpoint. Plasma NfL was measured at baseline and week 24 using Simoa technology. Results: At baseline, median plasma NfL was 12.33, 12.33, and 11.69 pg/mL for ozanimod 0.5 mg, ozanimod 1.0 mg, and placebo, respectively. Higher baseline NfL was associated with greater baseline gadolinium-enhancing lesion counts and T2 lesion volume. Median plasma NfL at week 24 was 9.39, 9.28, and 11.77 pg/mL, respectively. The decrease in NfL levels from baseline to week 24 differed significantly for ozanimod 0.5 mg (p=0.0048) and 1.0 mg (p=0.0087) vs. placebo. Relative to placebo, both ozanimod doses reduced the mean cumulative numbers of gadolinium-enhancing (both p Conclusions: Both ozanimod doses significantly reduced NfL levels between baseline and week 24 by 25% vs. placebo. These declines may correlate with the clinically significant reductions in new gadolinium-enhancing and new/enlarging T2 lesion development over weeks 12–24 seen with ozanimod. These data suggest that plasma NfL is a biomarker of brain lesion activity, but additional studies are needed. Study Supported by: Celgene Disclosure: Dr. Taylor Meadows has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Taylor Meadows holds stock and/or stock options in Celgene, which sponsored research in which Dr. Taylor Meadows was involved as an investigator. Dr. Taylor Meadows has received research support from Celgene. Dr. Skolnick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Frohna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Aranda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene. Dr. Southworth has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with celgene, GSk, astrazeneca, ardea, university of Manchester, university of Lancaster, clarostat Ltd, alphamedstat ltd, stone biostatistics Ltd, allecra. Dr. Opiteck has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene.