Long-Term Ofatumumab Shows Promise for Treatment-Naïve Relapsing MS

First-line, continuous ofatumumab (Kesimpta; Novartis) treatment for up to 6 years in recently diagnosed treatment-naïve patients living with relapsing multiple sclerosis (MS) demonstrated sustained safety and efficacy, according to study results presented by Novartis at the 2024 American Academy of Neurology (AAN) annual meeting, held from April 13 to 18, 2024, in Denver, Colorado.

Researchers conducted an open-label extension study (ALITHIOS; ClinicalTrials.Gov Identifier: NCT03650114) to evaluate the long-term effects of ofatumumab in recently diagnosed (≤3 years) and treatment-naïve patients with relapsing MS.

In the first analysis, the core phase 3 trials of this study demonstrated a low annualized relapse rate of 0.104, which was reduced by 52.0% to 0.050 in the ALITHIOS study, corresponded to an adjusted annualized relapse rate (ARR) of 1 relapse per 20 years. Both 3- and 6-month rates of progression independent of relapse activity were lower among patients taking ofatumumab vs patients who switched from teriflunomide to ofatumumab later in the study.

Among patients who continuously used ofatumumab, the rapid increase in the proportion of patients with no evidence of disease activity was maintained up to 6 years.

Of the patients who were initially taking teriflunomide, switching to ofatumumab resulted in significant improvements in efficacy outcomes, including reductions in AAR (71.3%) and in magnetic resonance imaging (MRI) lesion activity (Gd+ T1: 98.5% reduction; neT2: 93% reduction), as well as increased rates of no evidence of disease activity (NEDA). 

While there were improved efficacy outcomes in patients switching to ofatumumab, rates of 3- and 6-month confirmed disability worsening events were higher in this group of patients vs those receiving continuous ofatumumab. Among patients in both groups, 9 out of 10 had NEDA by year 6.

Similar results were observed in the second analysis, which considered the overall population in ALITHIOS.

Ofatumumab was well-tolerated and demonstrated no additional safety signals for up to 6 years, with rates of adverse events (AE), serious AEs, serious infections, and malignancies remaining consistent. The most commonly reported AEs were infections, such as:

• COVID-19 (34.3%),
• nasopharyngitis (20.6%),
• upper respiratory tract infection (14.9%), and
• urinary tract infection (14.4%). 

The average serum immunoglobulin (Ig) G levels were consistent up to 6 years of treatment, with most patients (97.2%) having lgG levels above the lower limit of normal. While average serum IgM levels decreased over time, they remained above the lower limit of normal for most patients (65.9%).

“While measurable improvements were also seen in patients switching to Kesimpta later on, the delay in irreversible disability worsening was not fully realized in the switch group compared to those starting on Kesimpta first, reinforcing the value of introducing the treatment to patients earlier,” said principal investigator Gabriel Pardo, MD, Founding Director of the Multiple Sclerosis Center of Excellence at Oklahoma Medical Research Foundation, in a Novartis news release.