Ofatumumab Positively Impacts Neurofilament Light, NEDA Status Regardless of Race or Ethnic Background

Enrique Alvarez, MD, PhD

Recently presented data from the ALITHIOS open-label extension (NCT03650114) showed that ofatumumab (Kesimpta; Novartis), an FDA-approved disease-modifying therapy for relapsing multiple sclerosis (MS), is effective in reducing serum neurofilament light (sNfL) and improving no evidence of disease activity (NEDA) rates among various racial and ethnic subgroups.¹

Of the 1882 patients randomly assigned in phase 3 ASCLEPIOS I/II trials, 1367 (72.6%) participants entered ALITHIOS, the OLE, and received ofatumumab for up to 5 years. Of these, 46 were Asian, 31 Black, 105 Hispanic, 1142 White, and 43 other. The data, presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 2, in Nashville, Tennessee, included summary statistics of these groups due to small numbers.

Led by Enrique Alvarez, MD, PhD, an associate professor of neurology at the University of Colorado School of Medicine, data were analyzed for up to 5 years in those randomly assigned to ofatumumab who continued on treatment throughout the OLE (OMB-OMB group) as well as those who switched from teriflunomide (Aubagio; Sanofi), the comparator drug, to ofatumumab in ALITHIOS (TER-OMB). At year 5, 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 in the OMB-OMB group.

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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NEDA-3 rates at year 1/ year 5 in the OMB-OMB group were 48.3%/91.7%, 52.2%/85.7%, 50.0%/98.4%, 47.9%/93.3%, and 40.5%/89.3% in the Asian, Black, Hispanic, White, and Other subgroups, respectively. In the TER-OMB group, NEDA-3 rates at year 1/year 5 by ethnicity were 32.4%/96.7%, 13.8%/78.9%, 30.0%/97.5%, 24.7%/90.2%, and 30.0%/100%, respectively. Authors concluded that these data support the idea behind earlier initiation of high-efficacy therapy in patients with relapsing MS irrespective of racial/ethnic background.

Ofatumumab, a subcutaneous injection therapy, was approved by the FDA in 2020 based on data from ASCLEPIOS I and II. The studies, which feature more than 1800 patients, pitted the agent against teriflunomide, an oral inhibitor of pyrimidine synthesis that reduces T-cell and B-cell activation. In the studies results showed a 51% reduction in annualized relapse rate (ofatumumab: 0.11; teriflunomide: 0.22; difference, −0.11; 95% CI, −0.16 to −0.06; P <.001) in ASCLEPIOS I and 58% (ofatumumab: 0.10; teriflunomide: 0.25; difference, −0.15; 95% CI, −0.20 to −0.09; P <.001) reduction in ASLCEPIOS II in those who received ofatumumab.²

More recently, at the 2024 American Academy of Neurology (AAN) Annual Meeting, data from the 3 studies showed that ofatumumab maintains efficacy over a 6-year treatment course among those with treatment-naïve relapsing MS. Findings showed patients treated with ofatumumab had 44% fewer relapses as well as had a 96.4% and 82.7% reduction in MRI lesions (Gd+ T1 and neT2), respectively, compared with those who switched from teriflunomide (Aubagio; Sanofi Genzyme) to ofatumumab. In the same treatment group, results showed patients had 24.5% and 21.6% fewer 3- and 6-month confirmed disability worsening (CDW) events, respectively, compared with the switch group.³

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REFERENCES
1. 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.
2. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020;383:546—557. doi: 10.1056/NEJMoa1917246
3. Pardo G, Hauser S, Bar-Or A, et al. Longer-term (Up to 6 Years) Efficacy of Ofatumumab in People with Recently Diagnosed and Treatment-naive Relapsing Multiple Sclerosis. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.