Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS) (S24.002)

Objective: To provide interim analysis of the ocrelizumab cerebrospinal fluid (CSF) and blood biomarker study (OBOE, NCT02688985) in multiple sclerosis (MS).

Background: CSF biomarkers, including neurofilament light chain (NfL) and lymphocyte numbers, are potential indicators of central nervous system status and may improve understanding of MS disease pathways and therapeutic mechanisms of action.

Design/Methods Patients with relapsing (RMS) or primary progressive MS receive ocrelizumab 600 mg every 24 weeks. CSF is obtained by lumbar puncture (LP) before and at 12, 24, or 52 weeks after ocrelizumab treatment; an RMS control arm receives 2 LPs 12 weeks apart before starting ocrelizumab. Biomarkers are reported in RMS patients with pre-ocrelizumab and 12-week (Arm 1) and 24-week (Arm 2) post-ocrelizumab CSF available for interim analysis as of a June 1, 2017 clinical cutoff date (n=40). Safety data for all enrolled patients as of the cutoff is presented (n=82).

Results: CSF samples from Weeks 12 and 24 post-ocrelizumab treatment exhibited reductions in median concentration of NfL (−24%, −47%); median number of CD19⁺ B cells (−86%, −82%) and median number of CD3⁺ T cells (−60%, −67%). Ocrelizumab was generally well tolerated, consistent with safety in the Phase 3 studies. Infusion-related reactions (44%) and 1 serious adverse event (seizure) were reported. No serious infections, malignancies or deaths were reported.

Conclusions: NfL decreased at 12 weeks, appeared to decrease further at 24 weeks, and correlated with CSF B and T cell numbers, suggesting continued reduction in axonal injury with ocrelizumab treatment, and that levels of CSF inflammatory cells may predict neuronal injury. A single dose of ocrelizumab reduced but did not completely deplete CSF B cells while also reducing CSF T cells, indicating B cells may function in T-cell antigen presentation, recruitment and/or maintenance in the CSF. The trial is continuing, with final results expected in early 2019.

Study Supported by:

Sponsored by Genentech, Inc.

Disclosure: Dr. Bar-Or has nothing to disclose. Dr. Gelfand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with . Dr. Fiore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Harp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Zheng has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Compensation from Genentech and stock in F. Hoffmann-La Roche Ltd as Genentech employee. Dr. Herman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Musch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Cross has received personal compensation for activities with AbbVie, BAYER, Biogen, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, and Teva. Dr. Cross has received research support for Genentech/ Roche.