AGNOS Study Results Demonstrate Ofatumumab’s Impact on Neurofilament Light, GFAP

New data from AGNOS, an ongoing, 18-month, phase 4 trial (NCT05084638) showed that treatment with ofatumumab (Kesimpta; Novartis) led to effective reductions on biomarkers of neuroaxonal damage in patients with relapsing-remitting multiple sclerosis (RRMS). The findings, which included positive changes in neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), further supported ofatumumab as a first-line therapy in early RRMS.¹

In this open-label study, patients aged 18-35 with treatment-naïve RRMS received monthly 20 mg subcutaneous ofatumumab for an 18-month period, using achievement of no evidence of disease activity (NEDA) status 3 as the primary outcome. Presented at the 2026 Americas Committee for Treatment & Research in Multiple Sclerosis (ATCRIMS), held February 5-7 in San Diego, the analysis focused on exploratory objectives like serum NfL and GFAP, with samples collected weekly at weeks 0 to 4 and monthly at M3, M6, M12, and M18.

A total of 180 patients were enrolled, including 119 in the ofatumumab group and 61 healthy controls, with a mean age of 28.1 years in the ofatumumab group and 27.4 years in controls. Among treated patients, the mean time from RRMS diagnosis to first ofatumumab dose was 0.19 years and from first symptoms to treatment was 1.08 years, with a baseline Expanded Disability Status Scale (EDSS) score of 1.70.

Led by Barry A. Hendin, MD, a board-certified neurologist at the Integrated MS Center in Arizona, mean serum NfL levels in the ofatumumab group declined from 20.66 pg/mL at baseline to 10.54 pg/mL at month 6 and remained stable at 11.05 and 10.20 pg/mL at months 12 and 18, respectively. In healthy controls, sNfL levels were lower and relatively stable over time, measuring 7.96 pg/mL at baseline and ranging from 8.03 to 9.29 pg/mL through month 18.

In the analysis, mean serum GFAP levels in the ofatumumab group decreased from 23.17 pg/mL at baseline to 20.36 pg/mL at month 6 and remained stable at 20.57 and 21.22 pg/mL at months 12 and 18, respectively. In healthy controls, sGFAP concentrations were lower and relatively unchanged over time, measuring 15.35 pg/mL at baseline and ranging from 14.51 to 15.25 pg/mL through month 18.

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In MS, serum GFAP and NfL have served as complementary biomarkers reflecting different aspects of central nervous system injury. NfL is released with axonal damage and correlates with inflammatory activity, relapses, MRI lesion burden, and treatment response, making it a useful marker of ongoing neuroaxonal injury. GFAP, an astrocytic structural protein, is more closely associated with astroglial activation and chronic tissue damage, and has been linked to progressive disease biology and disability accumulation.

Ofatumumab, a fully human anti-CD20 monoclonal antibody, was approved in 2020 as a treatment for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Its approval was supported by the phase 3 ASCLEPIOS I and II trials (NCT02792218; NCT02792231), where it significantly reduced annualized relapse rate, MRI lesion activity, and risk of confirmed disability worsening compared with teriflunomide (Aubagio; Sanofi), another approved disease-modifying therapy.²

A phase 3 extension to the ASCLEPIOS trials, dubbed ALITHIOS (NCT03650114), first showed ofatumumab’s effect on serum NfL. Presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, data were analyzed for up to 5 years in those randomly assigned to ofatumumab who continued on treatment throughout the OLE as well as those who switched from teriflunomide.³

At year 5 of the study, investigators recorded lower mean sNfL levels in Asian (baseline to yr 5: 13.1 to 8.5 pg/mL) Black (10.9 to 7.2 pg/mL), Hispanic (11.9 to 8.1 pg/mL), White (10.9 to 8.9 pg/mL), and Other (12.3 to 8.9 pg/mL) subgroups for those who continued ofatumumab all the way through. For those who switched, lower sNfL levels remained across Asian, Black, Hispanic, White, and Other subgroups (10.8 to 7.4 pg/mL; 11.4 to 9.5 pg/mL; 9.9 to 8.5 pg/mL; 10.6 to 9.2 pg/mL; 12.9 to 8.3 pg/mL, respectively). In addition, higher NEDA-3 rates were achieved earlier across all racial/ethnic subgroups in the continuous vs switch groups and were consistent with those of the overall population.

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REFERENCES
1. Hendin B, Wray S, Chinea A, et al. P067 / P067 - Effect of Ofatumumab on NfL and GFAP Levels in Treatment-Naïve Patients With Early Relapsing Multiple Sclerosis: Results From the AGNOS Study. Presented at: 2026 ACTRIMS Forum; February 5-7; San Diego, CA. ABSTRACT P067.
2. FDA approves Novartis Kesimpta® (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. News release. Novartis. August 20, 2020. Accessed February 6, 2026. https://www.globenewswire.com/news-release/2020/08/20/2081597/0/en/FDA-approves-Novartis-Kesimpta-ofatumumab-the-first-and-only-self-administered-targeted-B-cell-therapy-for-patients-with-relapsing-multiple-sclerosis.html
3. Alvarez E, Pardo G, Okai AF, et al. Serum Neurofilament Light Chain Levels and NEDA-3 Status With Ofatumumab Treatment in Diverse Racial/Ethnic Subgroups With Relapsing Multiple Sclerosis: 5-Year Results From ALITHIOS.