AAN 2023: MS disability not worse for most on Kesimpta over 5 years
Therapy for relapsing MS also shows good safety in new trial data
More than 80% of patients with relapsing forms of multiple sclerosis (MS) given Kesimpta (ofatumumab) continuously for up to five years in a clinical trial did not have any documented worsening of disability over the duration of the treatment.
That’s according to new data from the ongoing ALITHIOS study (NCT03650114), which were presented this week at the American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27 in Boston and virtually.
“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,” Victor Bultó, president of innovative medicines U.S. at Novartis, said in a company press release.
Jeffrey A. Cohen, MD, the study’s principal investigator at the Neurological Institute at Cleveland Clinic, presented the new findings in a talk titled, “Effect of Longer-term Ofatumumab Treatment on Disability Worsening and Brain Volume Change.” The work was led by Novartis, which markets Kesimpta.
“The five-year data support the long-term tolerability and safety of treatment with Kesimpta,” Cohen said in an email to Multiple Sclerosis News Today.
Trials investigating Kesimpta’s effect on long-term MS disability
Kesimpta is an approved treatment for relapsing types of MS that works to deplete B-cells, a type of immune cell implicated in the autoimmune attack that drives the neurodegenerative disease. It is given monthly via subcutaneous (under-the-skin) injection, which can be done at home.
Novartis sponsored a pair of Phase 3 clinical trials, called ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), that tested Kesimpta against the older MS therapy Aubagio (teriflunomide).
The studies enrolled 1,882 people with relapsing-remitting MS (RRMS) or active secondary progressive MS (SPMS), who were followed for up to 2.5 years.
Findings from the trials, which supported approvals of Kesimpta, showed that rates of relapses and disability progression were significantly lower among patients administered Kesimpta compared with those given Aubagio.
After the ASCLEPIOS trials ended, 1,367 participants (72.6%) chose to enter ALITHIOS, an open-label extension study in which all participants are being treated with Kesimpta and followed for long-term outcomes.
Among the participants in ALITHIOS, 690 had been on Kesimpta in the original ASCLEPIOS trials, while the other 677 switched from Aubagio to Kesimpta upon entering the extension study.
New findings showed that, after up to five years of total follow-up, the rate of confirmed disability worsening was lower among patients given continuous Kesimpta (17.7%), compared with those who first started on Aubagio (20.3%).
This meant that more than 80% of people who were always on Kesimpta and nearly 80% of those who switched had no reported worsening of disability over the duration of treatment. In the extension part alone, about 92% of patients in both groups experienced no confirmed disability worsening.
Continuous treatment with Kesimpta was associated with reduced risk of disability worsening and low brain volume change compared to switching to Kesimpta after initial treatment with [Aubagio].
Disability progression can occur due to incomplete recovery from relapses — known as RAW — or it can be independent of relapse activity, which is called PIRA. In the trial, most of the disability progression events occurred in the absence of disease relapses, but the continuous Kesimpta group had lower rates of both RAW and PIRA.
“The majority of disability worsening events were due to PIRA, ranging from 65-70% in the two treatment groups, far exceeding the amount of worsening related to incomplete recovery from relapses,” Cohen said.
“Of the various types of confirmed disability worsening, the continuous [Kesimpta] group had superior efficacy as compared to the [Aubagio] group,” he added.
Treatment with Kesimpta known to suppress immune system
In the original ASCLEPIOS trials, patients treated with Kesimpta had a markedly slower rate of brain atrophy (shrinkage) compared with those on Aubagio — 0.34% vs. 0.42% per year — though the difference was not statistically significant in the original studies.
During the ALITHIOS extension, the average rate of brain atrophy was comparable, according to investigators, for patients on continuous Kesimpta (0.27% per year) and those who switched from Aubagio (0.28% per year).
By the five-year mark, the total amount of accumulated brain atrophy was lower among patients given continuous Kesimpta, who on average lost less than 1.5% total brain volume over this time.
“Continuous treatment with Kesimpta was associated with reduced risk of disability worsening and low brain volume change compared to switching to Kesimpta after initial treatment with [Aubagio],” Cohen said, adding, “Outcomes favored earlier, compared with later initiation with Kesimpta.”
In a separate poster presentation at the AAN meeting, scientists shared long-term safety findings from the ALITHIOS study. That poster was titled, “Five-Year Safety of Ofatumumab in People Living With Relapsing Multiple Sclerosis.”
These results showed the long-term safety profile of Kesimpta was consistent with findings from the original Phase 3 trials. The most common safety-related events associated with the immune-suppressing medication were infections, including the common cold, urinary tract infections, and COVID-19.
“New long-term data from the ALITHIOS open-label extension showed Kesimpta maintained a similar safety profile as seen in the pivotal Phase 3 ASCLEPIOS I and II trials up to five years of treatment, with no new safety risks identified over the treatment period,” Cohen said.
More than 90% of infections resolved without stopping Kesimpta treatment. Among COVID-19 infections specifically, 92.3% were deemed non-serious, and 98.5% of patients recovered or were recovering from the infection, according to researchers.
Levels of antibodies, or infection-fighting proteins in the body, were above the lower limit of normal in almost all patients on long-term Kesimpta, the data showed.
“No increased risk of serious infections (excluding COVID-19) was observed over five years of Kesimpta treatment,” Cohen said.
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.
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