Mayzent Aids Cognitive Processing Speed in SPMS Patients, Trial Suggests

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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cognition and MS

Mayzent (siponimod) significantly improved cognitive processing speed in people with secondary progressive multiple sclerosis (SPMS) compared with a placebo, according to additional analyses of two-year data from the EXPAND Phase 3 trial.

While no approved therapies in the U.S. currently target cognitive impairment in MS, “our study found that [Mayzent], which is prescribed to slow the progression of physical disability in MS, may also help improve cognitive processing speed in people with advanced MS,” Ralph H. B. Benedict, PhD, the study’s first author, said in a press release.

Benedict is a professor of neurology at the University of Buffalo in New York, and a member of the American Academy of Neurology. 

Since significant improvements were seen in only one of the three cognitive function tests included in the trial, “more research should further examine how [Mayzent] affects scores on a broader array of thinking and memory tests,” Benedict added.

These findings were reported in the study, “Siponimod and cognition in secondary progressive multiple sclerosis: EXPAND secondary analyses,” published in the journal Neurology.

Cognitive difficulties are estimated to affect a vast majority of MS patients, and are usually more severe in progressive than in relapsing forms of the disease. Impairment is associated with a considerable negative impact on patients’ quality of life, with processing speed as the most commonly affected cognitive domain.

Cognitive processing speed is the amount of time it takes a person to take in information, process it, and then react to solve a problem or complete a task.

Mayzent, developed by Novartis, is an oral treatment approved in the U.S. for adults with clinically isolated syndrome, relapsing-remitting MS, and active SPMS. 

Its approval was largely based on results from the ongoing EXPAND Phase 3 trial (NCT01665144), which showed that a two-year treatment with Mayzent (2 mg tablets given once daily) was superior to placebo at lowering the risk of disability progression in 1,651 SPMS patients.

Participants completing the placebo-controlled part of the trial, lasting up to three years, had the option to enter its long-term, open-label extension part, in which all would be given Mayzent.

Now, in a Novartis-funded study, researchers evaluated the effects of treatment on patients’ cognitive function over the first two years of the trial’s placebo-controlled phase.

EXPAND participants underwent cognitive assessments before the start of treatment and every six months thereafter. Cognitive skills were assessed using the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) to measure cognitive processing speed, as well as the Brief Visuospatial Memory Test-Revised (BVMT-R) for visual or spatial memory.

Of note, SDMT is the gold standard measure of cognitive processing speed, and a score change of at least four points is considered clinically meaningful.

Results showed a significant improvement in SDMT scores among Mayzent-treated patients after one year, one-and-a-half years, and two years of treatment, compared with those given a placebo — whose scores remained stable.

Based on SDMT scores, the therapy was found to be superior to placebo at lowering patients’ risk of a sustained, clinically meaningful worsening in cognitive processing speed — by 21% — and at increasing their chances of a confirmed improvement (a four-point sustained increase in SDMT scores) — by 28%.

A greater proportion of Mayzent-treated patients also showed clinically meaningful improvements in SDMT scores (35% vs. 27% in the placebo group), while a smaller proportion had clinically meaningful worsening (25% vs. 32%). No changes in scores were reported for 41% of the Mayzent group and 42% of the placebo group. No significant group differences were found for PASAT and BVMT-R scores.

Overall, these findings highlighted that Mayzent had “a significant benefit on SDMT in SPMS patients,” the researchers wrote.

They noted, however, that the study had some limitations, including the lack of a systematic collection of data regarding education and MS symptoms, such as fatigue and depression, which may affect participants’ cognition and the study’s findings.

Still, these positive results are consistent with EXPAND’s five-year data, showing that patients randomized to Mayzent at the trial’s start were 23% less likely to show SDMT score worsening than were those switching from placebo to Mayzent three years later, when entering the trial’s open-label extension.

“We are impressed to see that [Mayzent] may improve cognitive processing speed in people with MS,” Benedict said, but “more research is needed to confirm our results” and “before prescribing [Mayzent] for cognition can be considered.”

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