Ocrelizumab Treatment Associated with Significant Decreases in Blood Levels of Neurofilament Light

Biomarker data from the ORATORIO and OPERA I clinical trials (NCT01194570 and NCT01247324) of ocrelizumab (Ocrevus; Genentech, South San Francisco, CA) for relapsing and primary progressive multiple sclerosis (MS) were presented at the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS) in Stockholm, Sweden September 11-13, 2019. 

In individuals with MS, treatment with ocrelizumab was associated with reduction of blood neurofilament light (NfL) levels to a range similar to that seen in healthy individuals. A byproduct of axonal neurodegeneration, NfL is being studied as a potential biomarker for multiple neurodegenerative diseases.

Individuals with relapsing MS who were treated with ocrelizumab over 96 weeks had a 43% reduction in blood NfL levels compared with a 31% reduction in participants treated with interferon beta-1a (IFN) (P < .001). People with primary progressive MS who were treated with ocrelizumab had a 16% reduction in blood NfL levels compared with a 0.2% reduction in individuals treated with placebo (P < .001).

At 96 weeks, individuals with primary progressive MS who had higher blood levels of NfL upon study enrollment had greater disability progression in upper and lower limbs. Additionally, overall disability was correlated with higher blood levels of NfL for individuals with RMS treated with IFN.  

In the phase 3 OBOE study (NCT02688985), individuals with primary progressive MS who had active gadolinium-enhancing T1 lesions also had median cerebrospinal fluid (CSF) NfL levels that were twice that of individuals without those lesions; higher NfL levels in people with relapsing MS with active lesions has been previously reported as well. 

“These analyses from the Ocrevus trials strengthen the evidence for pursuing NfL as a potential biomarker of disease activity and progression in MS, including its potential to predict future disability outcomes,” said Amit Bar-Or, M.D., FRCP, FAAN, FANA, chair of the Scientific Steering Committee of the OBOE study and chief of the Multiple Sclerosis Division of the Department of Neurology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. “Disease progression in MS can be challenging to identify without noticeable relapses or disability progression, and continued investigation into neurofilament light chain may help us better understand the underlying progression in all forms of this disease.”