A new study of first-line continuous Kesimpta treatment suggests sustained effectiveness for up to six years in treatment-naïve people recently diagnosed with relapsing multiple sclerosis.

Outcome effectiveness included 44 percent fewer relapses; 96.4 percent and 82.7 percent reductions in MRI lesions, respectively; and 24.5 percent and 21.6 percent fewer three- and six-month confirmed disability worsening events, respectively, versus those who switched to Kesimpta (ofatumumab) from teriflunomide. A separate analysis of the overall study population showed similar efficacy with continuous Kesimpta treatment, which was also well-tolerated with a consistent safety profile for up to six years.

In the first analysis, the low annualized relapse rate experienced by the recently diagnosed – defined as starting treatment within three years of initial diagnosis – treatment-naïve people living with RMS receiving continuous Kesimpta during the core Phase III trials was further reduced in the ALITHIOS open-label extension study by 52 percent, corresponding to an adjusted annualized relapse rate of one relapse per 20 years. Rates of three- and six-month progression independent of relapse activity with first-line Kesimpta were also lower versus switch. The observed rapid increase in the proportion of participants with no evidence of disease activity with continuous first-line Kesimpta treatment was maintained up to six years.

In recently diagnosed treatment-naïve people living with RMS initially randomized to teriflunomide, improvements across several efficacy outcomes were seen after switching to Kesimpta, including significant reductions in annualized relapse rate, MRI lesion activity, and rapid increase in rates of no evidence of disease activity. However, rates of three- and six-month confirmed disability worsening events remained higher as compared to patients receiving continuous Kesimpta, indicating that the efficacy benefit of first-line Kesimpta on delaying disability worsening was not fully achieved in the switch group. Across both continuous and switch groups, nine out of 10 participants achieved no evidence of disease activity at year six.

Similar results were seen in the second analysis, which looked at the overall ALITHIOS population. Findings showed sustained efficacy of continuous Kesimpta up to six years, including low annualized relapse rate, suppression of MRI lesion activity, sustained reduction of six-month confirmed disability worsening events, lower rates of six-month progression independent of relapse activity, and sustained high rates of no evidence of disease activity. People switching from teriflunomide to Kesimpta experienced reductions in annualized relapse rate and MRI lesion activity and a rapid increase in no evidence of disease activity rates during the extension period. Six-month confirmed disability worsening rates remained higher compared to patients receiving continuous Kesimpta, again highlighting an efficacy benefit of first-line Kesimpta on delaying disability worsening that was not fully achieved in the switch group. At year six, no evidence of disease activity status was achieved in nine out of 10 participants in both the continuous and switch groups.

The study also found that treatment with Kesimpta for up to six years was well-tolerated with no unexpected safety signals identified. The rates of adverse events, serious adverse events, serious infections, and malignancies remained stable with no increased risks over six years.

The overall rates of adverse events and serious adverse events up to six years of Kesimpta treatment were consistent between the core Phase III trials and the ALITHIOS extension study. The most common adverse events were infections: COVID-19 (34.3 percent), nasopharyngitis (20.6 percent), upper respiratory tract infection (14.9 percent), and urinary tract infection (14.4 percent). The incidence of serious infections remained stable over time and did not increase with Kesimpta treatment up to six years.

Average serum immunoglobulin G levels remained stable up to six years of treatment and the majority of patients had lgG levels above the lower limit of normal. Mean serum immunoglobulin M levels decreased over time but remained above the lower limit of normal for the majority of patients. No link was observed between IgG/IgM levels below the lower limit of normal and risk of serious infections.

The findings were presented at the American Academy of Neurology 2024 Annual Meeting held in Denver.