Ocrelizumab treatment reduced levels of neurofilament light chain and numbers of B cells in the cerebrospinal fluid of patients with relapsing multiple sclerosis in the OBOE study (S56.008)

Objective: To provide interim analysis (IA) results from the relapsing multiple sclerosis (RMS) cohort of OBOE (Ocrelizumab Biomarker Outcome Evaluation; NCT02688985), a cerebrospinal fluid (CSF) and blood biomarker study. Background: Serum and CSF levels of neurofilament light chain (NfL) and CSF lymphocyte numbers are emerging biomarkers of axonal damage and inflammation, respectively. Responses of these biomarkers to ocrelizumab (OCR) may improve the understanding of MS pathophysiology and therapeutic mechanism of action. Design/Methods: Patients with RMS received OCR 600-mg infusions every 24 weeks. CSF samples were obtained by lumbar puncture (LP) before OCR and at 12, 24 or 52 weeks after initial OCR treatment. Patients in a nonrandomized RMS reference arm underwent two LPs 12 weeks apart prior to initiation of OCR. The primary endpoint is change in CSF NfL levels and lymphocyte numbers between pre- and post-treatment time points. All enrolled patients (n=100) are included in this IA. Results: Pretreatment CSF and serum NfL levels correlated strongly (r=0.78; p Conclusions: In RMS patients, ocrelizumab significantly decreased CSF/serum NfL and CSF B cells, suggesting that treatment reduces ongoing axonal injury and compartmentalized CNS inflammation. CSF B cells were almost completely depleted in most patients at Weeks 12, 24 and 52, whereas CSF T cells were moderately reduced in many but not all patients. Disclosure: Dr. Cross has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Celgene, EMD Serono, Genzyme, Genentech, Novartis. Dr. Cross has received research support from Genentech. Dr. Bennett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Clene Nanomedicine, EMD Serono, Equillium Inc, Frequency Therapeutics, and Viela Bio. Dr. Bennett has received research support from EMD Serono. Dr. Von Budingen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Carruthers has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. Dr. Carruthers has received research support from Teva Innovation Canada, Roche Canada. Dr. Edwards has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, EMD Serono. Dr. Edwards has received research support from Biogen, Eli Lilly, Genentech, Genzyme/Sanofi, Hoffmann-La Roche, and Novartis. Dr. Fallis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono. Dr. Fiore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Gelfand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Medimmune, Quest Diagnostics, and government and commercial entities for medical legal consulting. Dr. Gelfand has received personal compensation in an editorial capacity for Dynamed. Dr. Gelfand has received research support from Genentech and MedDay. Dr. Giacomini has nothing to disclose. Dr. Greenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Alexion, EMD Serono. Dr. Greenberg has received research support from Chugai, Medimmune, Genentech, MedDay, PCORI, NIH, NMSS and Guthy Jackson Charitable Foundation for NMO. Dr. Hafler has nothing to disclose. Dr. Harp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech Inc. Dr. Assman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Herman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Inc. Dr. Ionete has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. Ionete has received research support from Biogen, Roche, and Sanofi. Dr. Kaunzner has nothing to disclose. Dr. Lock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Sanofi Genzyme. Dr. Ma has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Inc. Dr. Musch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Pardo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva. Dr. Piehl has nothing to disclose. Dr. Weber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen-Idec, Merck Serono, Novartis, Roche, TEVA, Bayer and Genzyme. Dr. Weber has received research support from Deutsche Forschungsgemeinschaft, Novartis, TEVA, Biogen-Idec, Roche, Merck and the ProFutura Program of the Universitatsmedizin Gottingen. Dr. Ziemssen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Biogen Idec, Novartis, Merck Serono, Teva, Genzyme, Synthon, Merck Sharp & Dohme, GlaxoSmithKline, Sanofi, and Almirall. Dr. Ziemssen has received research support from Bayer Healthcare, Biogen, Genzyme, Novartis, Teva, and Sanofi. Dr. Bar-Or has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Dr. Bar-Or has received research support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.