Ofatumumab Shows Long-term Safety and Efficacy, Does Not Restrict COVID-19 Vaccine Immune Response

Lykke Hinsch Gylvin, MD, EMBA

New safety data from the ongoing, open-label, umbrella extension ALITHIOS trial (NCT03650114) and the phase 3 ASCLEPIOS I/II trials (NCT02792218 and NCT02792231) of ofatumumab (Kesimpta; Novartis) in patients with multiple sclerosis (MS) suggest that the therapy is well-tolerated with long-term use, showing no new safety signals.¹

Presented by Stephen L. Hauser, MD, director, University of California, San Francisco Weill Institute for Neuroscience, at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, they noted that “[these] additional safety data will help confirm ofatumumab’s longer-term safety profile and provide further confidence to the MS community.”

Data from ALITHIOS suggest that after up to 3.5 years of treatment, there was a low incidence of serious infections (2.9%; exposure-adjusted incidence rate [EAIR], 1.4) and malignancies (0.6%; EAIR, 0.3) among those with adverse events (AEs; ≥1 AE, 83.8%; EAIR, 148.7) and serious AEs (≥1 serious AE, 9.7%; EAIR, 4.8). After up to 4 years of treatment, levels of immunoglobulin G (IgG) were stable in ofatumumab-treated patients, while immunoglobulin M (IgM) decreased, though levels remained within normal ranges. Additionally, there were no associations identified between antibody levels and the risk of serious infection.¹

Long-term efficacy data, also presented by Hauser et al, suggest that over 4 years of use, the subcutaneous anti-CD20 monoclonal antibody was associated with fewer relapses, as well as a reduced risk of 3-month and 6-month confirmed disability worsening and less disease activity, compared with those who switched therapies.²

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Overall, 1882 patients randomized in the ASCLEPIOS I/II trials (ofatumumab, n = 946; teriflunomide, n = 936) were included in the efficacy analysis. Patients were a mean age of 38 years, and 68% were women. The mean Expanded Disability Status Scale (EDSS) score was 2.9, and the mean number of Gadolinium enhancing T1 lesions was 1.5 (SD, 3.9) and mean volume of T2 lesions was 13.2 cm³. Previously reported data showed superiority of ofatumumab versus teriflunomide in reducing annualized relapse rates (ARRs), as well as subduing MRI lesion activity. Overall, 690 patients treated with ofatumumab, and 677 patients treated with teriflunomide entered ALITHIOS.²

“We are pleased to share long-term data of up to four years that support Kesimpta as an efficacious and well-tolerated, first-choice option for people living with relapsing multiple sclerosis. The sustained reductions in disability progression and lesion activity observed in those receiving continuous Kesimpta versus those who switched later from teriflunomide highlight the value of earlier treatment initiation with Kesimpta,” Lykke Hinsch Gylvin, MD, EMBA, Neuroscience Global Medical Franchise Head, Novartis Pharmaceuticals, said in a statement.³

Those who finished the ASCLEPIOS I/II, APOLITOS (NCT03249714) and APLIOS (NCT03560739) clinical trials were eligible for ALITHIOS. The safety analysis included cumulative data in the overall cohort (n = 1969), as well as the continuous group (ofatumumab in core and extension; n = 1292) and newly switched group (teriflunomide core and ofatumumab extension; n = 677).¹

“In addition to these safety and efficacy data, we have presented findings that suggest people taking Kesimpta can mount an immune response to COVID-19 vaccination. During this pandemic, it is critical for people living with multiple sclerosis to have access to safe and efficacious treatments that do not interfere with their vaccine doses. Novartis is committed to continued research in multiple sclerosis with regards to COVID-19 vaccination and these data mark an additional milestone in this commitment,” Hinsch Gylvin added.³

Data from the ongoing KYRIOS open-label, prospective study showed that people living with multiple sclerosis on ofatumamab are able to produce an immune response to the COVID-19 mRNA vaccine.4 All participants in KYRIOS who were vaccinated during treatment developed an immune response as soon as the first week after their initial vaccination, and response in those who received a booster short during treatment was similar to those who received a booster before treatment.^3,4

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REFERENCES
1. Hauser SL, Cross AH, Winthrop K, et al. Long-term Safety of Ofatumumab in Patients With Relapsing Multiple Sclerosis. Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual.
2. Hauser SL, Fox E, Aungst A, et al. Long-term Efficacy of Ofatumumab in Patients With Relapsing Multiple Sclerosis. Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual.
3. Novartis presents new four-year data on efficacy and safety of Kesimpta® (ofatumumab) in people living with relapsing multiple sclerosis. News release. Novartis. April 5, 2022. Accessed April 8, 2022. https://www.novartis.com/news/media-releases/novartis-presents-new-four-year-data-efficacy-and-safety-kesimpta-ofatumumab-people-living-relapsing-multiple-sclerosis
4. Groth M, Ette B, Bopp T, Ziemssen T. Tracking the immune response to SARS-CoV-2 mRNA vaccines in an open-label multicenter study in participants with relapsing multiple sclerosis treated with ofatumumab s.c. (KYRIOS clinical trial). Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual.