Kesimpta (ofatumumab) six-year efficacy data show substantial benefits in recently diagnosed treatment-naïve people with relapsing multiple sclerosis – Novartis

Novartis announced new long-term data from the ALITHIOS open-label extension study showing that up to five years, patients treated earlier and continuously with Kesimpta (ofatumumab) had fewer disability worsening events and low brain volume change versus those who started on teriflunomide and were later switched to Kesimpta.

A separate analysis showed that treatment with Kesimpta for up to five years was well-tolerated, with no new or increased safety risks identified. These data will be presented at the American Academy of Neurology (AAN) Annual Meeting held in Boston and virtually on April 22-27, 2023.

“With continuous Kesimpta treatment, key indicators of disability progression and brain volume change showed that most patients remained free from disease progression up to five years,” said principal investigator Jeffrey A. Cohen, MD, of the Neurological Institute at Cleveland Clinic. “Outcomes favored earlier, compared with later, initiation of treatment with Kesimpta. Along with the five-year safety analysis, these data support this treatment as a well-tolerated, efficacious treatment option for people living with relapsing multiple sclerosis.”

In people with RMS who continued in the ALITHIOS study for up to five years, earlier treatment with Kesimpta was associated with fewer confirmed disability worsening (CDW) events, including progression independent of relapse activity and relapse associated worsening, versus those who switched later from teriflunomide. More than 80% of patients remained free of six-month CDW over the same five period.

Additionally, brain volume change remained low (less than 1.5% loss) with Kesimpta treatment over five years, and overall, patients initially randomized to Kesimpta had lower levels of brain volume loss at year five than those initially randomized to teriflunomide. Annual rate of brain volume change (ABVC) in the core Phase III trials for continuous Kesimpta was -0.34%/year and in the switch group, -0.42%/year (P=0.115). In the extension, ABVC in the Kesimpta group was -0.27%/year and in the switch group, -0.28%/year (P=0.666).

“These longer-term data continue to reinforce the favorable safety profile of Kesimpta, as well as its ability to slow disease progression, supporting its earlier use in people with relapsing multiple sclerosis,” said Victor Bultó, President, Innovative Medicines US, Novartis Pharmaceuticals Corporation. “Novartis remains committed to the multiple sclerosis community in our continued study of Kesimpta and to supporting those living with MS and their families throughout their journey.”

The separate analysis of the ALITHIOS extension data showed consistent safety results of Kesimpta for people with RMS following up to five years of treatment. The overall rates of adverse events (AEs) and serious AEs were consistent with the core Phase III trials. The most common AEs were infections (COVID-19 [30.3%], nasopharyngitis [19%], upper respiratory tract infection [12.8%] and urinary tract infection [12.7%]). Most COVID-19 cases were mild to moderate in severity (93.9%) and non-serious (92.3%), and 98.6% of patients treated with Kesimpta recovered, recovered with sequalae, or were recovering from COVID-19. Most (90.3%) infections resolved without discontinuing Kesimpta treatment.

The overall rate of serious infections also remained stable with no increased risk over five years (106 patients, or 5.38%, experienced serious infection in the core Phase III plus extension trials). Mean serum immunoglobulin G (IgG) levels remained stable up to five years of treatment and the majority of patients (98%) had lgG levels above the lower limit of normal (LLN). Mean serum immunoglobulin M (IgM) levels decreased over time but remained above the LLN for the majority of patients (69.4%). There was no association between reduction in Ig levels and risk of serious infections. Treatment interruption/discontinuation was reported in three (0.2%)/four (0.2%) patients due to low lgG; and 202 (10.3%)/71 (3.6%) patients due to low lgM. There were six fatal cases due to serious infections (five were COVID-19-related and one was due to pneumonia and septic shock).

16 April 2024-– Novartis announced data from the ALITHIOS open-label extension study showing sustained efficacy of first-line, continuous Kesimpta (ofatumumab) treatment for up to six years in recently diagnosed – defined as starting treatment within three years of initial diagnosis – treatment-naïve people living with relapsing multiple sclerosis (RMS). These efficacy outcomes included 44% fewer relapses; 96.4% and 82.7% reductions in MRI lesions (Gd+ T1 and neT2), respectively; and 24.5% and 21.6% fewer 3- and 6-month confirmed disability worsening (CDW) events, respectively, versus those who switched to Kesimpta from teriflunomide. A separate analysis of the overall ALITHIOS population showed similar efficacy with continuous Kesimpta treatment, which was also well-tolerated with a consistent safety profile up to six years. These data will be presented at the American Academy of Neurology (AAN) 2024 Annual Meeting held in Denver, Colorado and virtually on April 13-18, 2024.

“Our analysis of treatment-naïve people who were recently diagnosed with relapsing multiple sclerosis found that first-line use of Kesimpta for up to six years provided long-term benefits, including fewer relapses, profoundly suppressed MRI lesion activity, and fewer disability worsening events,” said principal investigator Gabriel Pardo, MD, Founding Director of the Multiple Sclerosis Center of Excellence at Oklahoma Medical Research Foundation. “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.”

Study Results : In the first analysis, the low annualized relapse rate (ARR) experienced by recently diagnosed treatment-naïve (RDTN) people living with RMS receiving continuous Kesimpta during the core Phase III trials was further reduced in the ALITHIOS open-label extension study, from 0.104 to 0.050 (52.0% reduction), corresponding to an adjusted ARR of one relapse per 20 years. Rates of 3- and 6-month progression independent of relapse activity (PIRA) with first-line Kesimpta were also lower versus switch. The observed rapid increase in the proportion of participants with no evidence of disease activity (NEDA-3) with continuous first-line Kesimpta treatment was maintained up to six years.

In RDTN people living with RMS initially randomized to teriflunomide, improvements across several efficacy outcomes were seen after switching to Kesimpta, including significant reductions in ARR (71.3%) and in MRI lesion activity (Gd+ T1: 98.5% reduction; neT2: 93% reduction), and rapid increase in rates of NEDA-3. However, rates of 3- and 6-month CDW events remained higher 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 NEDA-3 at Year 6.

Similar results were seen in the second analysis, which looked at the overall ALITHIOS population. Data showed sustained efficacy of continuous Kesimpta up to six years, including low ARR (49.9% reduction between core Phase III trials and extension phase), suppression of MRI lesion activity (Gd+ T1: 56.7% reduction; neT2: 89.3% reduction), sustained reduction of 6-month CDW events (14.1%, relative to the switch group), lower rates of 6-month PIRA, and sustained high rates of NEDA-3. People switching from teriflunomide to Kesimpta experienced reductions in ARR (73.8%) and MRI lesion activity (Gd+ T1: 97.7% reduction; neT2: 91.8% reduction) and a rapid increase in NEDA-3 rates during the extension period. Six-month CDW 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 6, NEDA-3 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 (AEs), serious AEs, serious infections, and malignancies remained stable with no increased risks over six years. The overall rates of AEs and serious AEs up to six years of Kesimpta treatment were consistent between the core Phase III trials and the ALITHIOS extension study. The most common AEs were infections (COVID-19 [34.3%], nasopharyngitis [20.6%], upper respiratory tract infection [14.9%], and urinary tract infection [14.4%]). The incidence of serious infections remained stable over time and did not increase with Kesimpta treatment up to six years.

Mean serum immunoglobulin G (IgG) levels remained stable up to six years of treatment and the majority of patients (97.2%) had lgG levels above the lower limit of normal (LLN). Mean serum immunoglobulin M (IgM) levels decreased over time but remained above the LLN for the majority of patients (65.9%). No clinically meaningful association was observed between IgG/IgM levels below the LLN and risk of serious infections.

Data from the ASCLEPIOS I/II core studies demonstrate Kesimpta’s efficacy and favorable safety and tolerability profile in RMS participants and the ALITHIOS open-label extension study provides additional support with up to 6 years of data. The at-home administration of Kesimpta by monthly doses of 20 mg/0.4mL with an autoinjector (Sensoready) also matches the preferences of many people living with MS due to its ease of use and supports patients to be compliant with, and persistent on the therapy over time. Kesimpta was originally developed by Genmab and licensed to GlaxoSmithKline; Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 2015 .Kesimpta has been approved for the treatment of relapsing forms of multiple sclerosis in over 90 countries worldwide with more than 100,000 patients treated as of March 2024.