Ocrelizumab Analyses of Neurofilament Light Levels Reveals Disease Progression Insights


New data from clinical trials of ocrelizumab showed that the anti-CD20+ B cell therapy lowered serum NfL levels, and that the NfL levels offered prognostic value for disease progression in MS.

Dr Amit Bar-Or

Amit Bar-Or, MD, FRCP, FAAN, FANA, chair, OBOE study Scientific Steering Committee, and chief, Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania

Amit Bar-Or, MD

New clinical trial data of ocrelizumab (Ocrevus, Genentech) have provided novel insight into the understanding of multiple sclerosis (MS) disease progression through the analysis of levels of biomarker neurofilament light chain (NfL), which it plans to present in Stockholm, Sweden, at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).1

Exposure to ocrelizumab resulted in a lowering of NfL levels to comparable to 118 healthy donors which established NfL ranges of 5.5—9.8 pg/mL for blood serum and 4.3–7.9 pg/mL for blood plasma. In this analysis, which included data from the phase 3 OBOE study, the donor range was defined as the 90th percentile of an age-matched healthy cohort.

“These analyses from the Ocrevus trials strengthen the evidence for pursuing neurofilament light chain as a potential biomarker of disease activity and progression in MS, including its potential to predict future disability outcomes,” said Amit Bar-Or, MD, FRCP, FAAN, FANA, chair, OBOE study Scientific Steering Committee, and chief, Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, in a statement.

READ NOW: Neurofilament Light Prognostic Value in MS Is Limited on Individual Level

Additionally, the phase 3 OPERA I and ORATORIO studies in relapsing MS and progressive MS, respectively, NfL levels were also significantly lower post-treatment with ocrelizumab. In relapsing MS, blood serum NfL levels were reduced by 43% from baseline to 96 weeks after treatment compared with a 31% reduction with interferon beta-1a (IFN β-1a ; P <.001), while in primary progressive disease, blood plasma NfL levels were reduced by 16% post-treatment compared with 0.2% reduction with placebo (P <.001).

“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,” Bar-Or said.

The Genentech agent, which targets CD20+ B cells, was shown to reduce brain MRI and relapse activity, as well as disability progression in patients in the OPERA and ORATORIO trials. Using the Quanterix Advantage Kit in patients with relapsing (OPERA I: treatment, n=368; IFN β-1a, n=347) and primary progressive disease (ORATORIO: treatment, n=347; placebo, n=169). The findings showed that both plasma and sera levels were strongly correlated (r = 0.94).

Of those with relapsing MS (n = 310) and primary progressive MS (n = 311) who had a baseline NfL level about the 90th percentile of a healthy donor, a higher proportion decreased within that range by Week 96 following ocrelizumab therapy compared to IFN-ß1a (relapsing MS: 81.4% vs. 58.9%; P <.001) and compared to placebo (primary progressive MS: 40.4% vs. 16.6%; P <.001).

Additionally, more elevated NfL levels at baseline were shown to be prognostic for more disability progression in primary progressive disease, as measured by the 9-hole peg test (hazard ratio [HR], 2.33; P = .036), timed 25-foot walk test (HR, 5.35; P = .003), and Expanded Disability Status Scale (EDSS) scores (HR, 1.84; P = .227). As well, higher baseline NfL was prognostic of worse disability outcomes in the relapsing MS group treated with IFN β-1a, similarly measured by 9-hole peg test (HR, 3.83; P = .16), timed 25-foot walk (HR, 1.07; P = .87), and EDSS (HR, 2.83; P = .024).

Ocrelizumab was the first, and remains the only, agent approved for relapsing MS, active secondary and primary progressive MS, in addition to clinically isolated syndrome (CIS), approved in 2017 in the United States. It is dosed every 6 months, with upward of 120,000 individuals treated globally.

For more coverage of ECTRIMS 2019, click here.


1. Genentech Presents New Ocrevus (Ocrelizumab) Biomarker Data That Increase Understanding of Disease Progression in Multiple Sclerosis at ECTRIMS [press release]. South San Francisco: Genentech; Published September 10, 2019. biospace.com/article/releases/genentech-presents-new-ocrevus-ocrelizumab-biomarker-data-that-increase-understanding-of-disease-progression-in-multiple-sclerosis-at-ectrims. Accessed September 10, 2019.

2. Bar-Or A, Thanei GA, Harp CT, et al. Blood neurofilament light levels are lowered to a healthy donor range in patients with RMS and PPMS following ocrelizumab treatment. Presented at: ECTRIMS; September 11—13, 2019; Stockholm, Sweden. Abstract 152.

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