Contributions
Abstract: EP1599
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Development of cerebrospinal fluid (CSF) biomarkers, such as neurofilament light chain (NfL) and/or lymphocyte cell signatures, may improve current understanding of multiple sclerosis (MS) pathogenesis and the therapeutic mechanism of action (MOA) of disease-modifying treatment (DMT). Ocrelizumab is a humanised monoclonal antibody that selectively targets CD20, a cell-surface antigen expressed on pre-B cells, mature B cells and memory B cells but not lymphoid stem cells or plasma cells. The Ocrelizumab Biomarker Outcome Evaluation study (OBOE; NCT02688985) aims to further elucidate the MOA of ocrelizumab in patients with relapsing MS (RMS) and primary progressive MS (PPMS) by examining potential biomarkers of neuronal or glial injury, B-cell antigen presentation, immunoglobulin production, cytokine secretion and meningeal inflammation.
Objective: To elaborate on the blood and CSF biomarkers being studied and the methodology for determining CSF cell signatures in OBOE.
Methods: The open-label OBOE study is enroling treatment-naive or previously treated patients with RMS or PPMS. All patients initially receive two intravenous (IV) infusions of ocrelizumab 300 mg separated by 14 days; at Weeks 24 and 48, patients with PPMS repeat this regimen, while patients with RMS receive single 600-mg infusions. Lumbar punctures to obtain CSF are performed prior to and at Month 3, 6 or 12 of ocrelizumab treatment; longitudinal CSF samples are also being collected from a subset of RMS patients while on DMT prior to receiving ocrelizumab. Freshly isolated CSF cells are examined using a standardized cell-surface phenotyping flow cytometry assay. Primary endpoints include changes in NfL, CD19+ B cells and CD3+ T cells in the CSF over 3, 6 and 12 months of ocrelizumab treatment.
Results: Planned enrolment includes 88 patients with RMS and 16 with PPMS; updated information on patient disposition will be presented. Assay development and approach to standardization of the multicenter CSF flow cytometry assay to limit analytical variability will be discussed.
Conclusions: OBOE will provide important information on putative disease biomarkers in the blood and CSF of patients with RMS and PPMS and the effects of selectively depleting CD20+ B cells on those markers. Findings are expected to improve understanding of the MOA of B-cell depletion in patients with MS.
Disclosure: Sponsored by Genentech, Inc.; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
A.H. Cross has served on scientific advisory boards for AbbVie, Biogen, EMD Serono, Race to Erase MS, Genentech/Roche, Genzyme/Sanofi, the Conrad N. Hilton Foundation, Mallinckrodt, Novartis and Teva.
A. Bar-Or has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Genentech, Inc., Biogen, GlaxoSmithKline, Merck/EMD Serono, MedImmune, Mitsubishi Tanabe, Ono, Receptos, Sanofi-Genzyme and Guthy-Jackson/GGF and has received research support from Novartis and Sanofi-Genzyme.
A. Herman is an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.
D. Fiore is an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.
C. Harp is an employee and shareholder of Genentech, Inc.
B. Musch is an employee and shareholder of Genentech, Inc.
Abstract: EP1599
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Development of cerebrospinal fluid (CSF) biomarkers, such as neurofilament light chain (NfL) and/or lymphocyte cell signatures, may improve current understanding of multiple sclerosis (MS) pathogenesis and the therapeutic mechanism of action (MOA) of disease-modifying treatment (DMT). Ocrelizumab is a humanised monoclonal antibody that selectively targets CD20, a cell-surface antigen expressed on pre-B cells, mature B cells and memory B cells but not lymphoid stem cells or plasma cells. The Ocrelizumab Biomarker Outcome Evaluation study (OBOE; NCT02688985) aims to further elucidate the MOA of ocrelizumab in patients with relapsing MS (RMS) and primary progressive MS (PPMS) by examining potential biomarkers of neuronal or glial injury, B-cell antigen presentation, immunoglobulin production, cytokine secretion and meningeal inflammation.
Objective: To elaborate on the blood and CSF biomarkers being studied and the methodology for determining CSF cell signatures in OBOE.
Methods: The open-label OBOE study is enroling treatment-naive or previously treated patients with RMS or PPMS. All patients initially receive two intravenous (IV) infusions of ocrelizumab 300 mg separated by 14 days; at Weeks 24 and 48, patients with PPMS repeat this regimen, while patients with RMS receive single 600-mg infusions. Lumbar punctures to obtain CSF are performed prior to and at Month 3, 6 or 12 of ocrelizumab treatment; longitudinal CSF samples are also being collected from a subset of RMS patients while on DMT prior to receiving ocrelizumab. Freshly isolated CSF cells are examined using a standardized cell-surface phenotyping flow cytometry assay. Primary endpoints include changes in NfL, CD19+ B cells and CD3+ T cells in the CSF over 3, 6 and 12 months of ocrelizumab treatment.
Results: Planned enrolment includes 88 patients with RMS and 16 with PPMS; updated information on patient disposition will be presented. Assay development and approach to standardization of the multicenter CSF flow cytometry assay to limit analytical variability will be discussed.
Conclusions: OBOE will provide important information on putative disease biomarkers in the blood and CSF of patients with RMS and PPMS and the effects of selectively depleting CD20+ B cells on those markers. Findings are expected to improve understanding of the MOA of B-cell depletion in patients with MS.
Disclosure: Sponsored by Genentech, Inc.; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
A.H. Cross has served on scientific advisory boards for AbbVie, Biogen, EMD Serono, Race to Erase MS, Genentech/Roche, Genzyme/Sanofi, the Conrad N. Hilton Foundation, Mallinckrodt, Novartis and Teva.
A. Bar-Or has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Genentech, Inc., Biogen, GlaxoSmithKline, Merck/EMD Serono, MedImmune, Mitsubishi Tanabe, Ono, Receptos, Sanofi-Genzyme and Guthy-Jackson/GGF and has received research support from Novartis and Sanofi-Genzyme.
A. Herman is an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.
D. Fiore is an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.
C. Harp is an employee and shareholder of Genentech, Inc.
B. Musch is an employee and shareholder of Genentech, Inc.