Study: Ofatumumab Shows Efficacy Up to 6 Years for Multiple Sclerosis

Ofatumumab (Kesimpta; Novartis) demonstrated a sustained efficacy as a first-line, continuous treatment for up to 6 years for those who were recently diagnosed and treatment-naïve with relapsing multiple sclerosis (MS). Further, the ALITHIOS trial (NCT03650114) showed that the overall population had similar efficacy compared to the continuous treatment, which was also well-tolerated with a consistent safety profile for up to 6 years.¹ The data were presented at the American Academy of Neurology 2024 Annual Meeting held in Denver, Colorado, from April 13 to April 18, 2024.¹

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According to the World Health Organization, there are over an estimated 1.8 million individuals with MS worldwide. MS can affect individuals of all ages, but is most common among young adults and females.²

“Our analysis of treatment-naïve [patients] who were recently diagnosed with relapsing [MS] found that first-line use of [ofatumumab] for up to 6 years provided long-term benefits, including fewer relapses, profoundly suppressed [magnetic resonance imaging (MRI)] lesion activity, and fewer disability worsening events,” said Gabriel Pardo, MD, founding director of the Multiple Sclerosis Center of Excellence at Oklahoma Medical Research Foundation, in a press release. “While measurable improvements were also seen in patients switching to [ofatumumab] later on, the delay in irreversible disability worsening was not fully realized in the switch group compared to those starting on [ofatumumab] first, reinforcing the value of introducing the treatment to patients earlier.”¹

According to the results, ofatumumab led to 44% fewer relapses, 96.4% and 82.7% reductions in MRI lesions for gadolinium-enhanced T1 and neT2, respectively, and 24.5% and 21.6% fewer 3- and 6-month confirmed disability worsening events, respectively, compared to placebo.¹ Additionally, the low annualized relapse rate (ARR) that was experienced by this patient population was further reduced from 0.104 to 0.050 with continuous ofatumumab with the open-label extension. Investigators found that rates of 3- and 6-month progression, independent of relapse activity with ofatumumab in the first line, were lower compared to individuals who switched to ofatumumab. The observed rapid increase of individuals with no evidence of disease activity was maintained up to 6 years, according to the press release.¹

For individuals who were initially randomized to teriflunomide, there were improvements across several efficacy outcomes, including reductions in ARR at 71.3% and in MRI lesion activity at 98.5% for gadolinium-enhanced T1, as well as 93% for neT2. Additionally, there were rapid increase in rates of no evidence of disease activity.¹

However, investigators noted that rates of 3- and 6-month confirmed disability worsening events were higher compared to those who received continuous ofatumumab. At 6 years, approximately 9 out of 10 patients across both groups achieved no evidence of disease activity.¹

In the second analysis of the overall population, the data showed the sustained efficacy of continuous ofatumumab up to 6 years, with a reduction in ARR of 49.9% between the initial phase 3 trials and the extension phase. Further, there were reductions in 56.7% gadolinium-enhanced T1 and 89.3% for neT2, sustained reduction of 6-month confirmed disability worsening events, lower rates of 6-month progression independent of relapse activity, and sustained high rates of no evidence of disease activity, according to the press release.¹

Furthermore, individuals who switched also experienced reductions in ARR and MRI lesion activity, as well as a rapid increase in no evidence of disease rates during the extension period. However, just like the other analysis, 6-month confirmed disability worsening events remained high.¹

The overall rates of adverse events (AEs) and serious AEs up to 6 years were consistent with the core phase 3 trials and the extension study, with the most common being infection. The incidence of serious infections was stable over time and did not increase with ofatumumab at up to 6 years of treatment.¹

References

1. Novartis Kesimpta six-year efficacy data show substantial benefits in recently diagnosed treatment- naïve people with relapsing multiple sclerosis. News release. Novartis. April 17, 2024. Accessed April 19, 2024. https://www.novartis.com/news/media-releases/novartis-kesimpta-six-year-efficacy-data-show-substantial-benefits-recently-diagnosed-treatment-naive-people-relapsing-multiple-sclerosis

2. World Health Organization. Multiple Sclerosis. August 7, 2023. Accessed April 19, 2024. https://www.who.int/news-room/fact-sheets/detail/multiple-sclerosis