Treatment with Mayzent (siponimod) provided sustained improvements and prevented deterioration of cognitive processing speed in patients with secondary progressive multiple sclerosis (SPMS), regardless of their cognitive function prior to therapy, according to results of a Phase 3 clinical trial.
The data were presented at the recent 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia (May 4-10), by Ralph Benedict, PhD, professor of neuropsychology at University at Buffalo. His poster was titled “Effect of Siponimod on Cognition in Patients with Secondary Progressive Multiple Sclerosis (SPMS): Phase 3 EXPAND Study Subgroup Analysis.”
Cognitive impairment affects about 50–70% of patients with multiple sclerosis (MS), and usually is more severe in progressive than in relapsing forms of the disease — with cognitive processing speed being the most commonly affected cognitive domain.
Positive results from the EXPAND Phase 3 trial (NCT01665144) were largely the basis of the recent approval of Novartis’s Mayzent oral tablets in the U.S. for adults with clinically isolated syndrome, relapsing-remitting disease, and active SPMS. Among other benefits reported in the study, Mayzent was shown to improve cognitive processing speed in patients with or without relapses (referring to active or non-active SPMS, respectively) within two years of treatment.
Now, in a subsequent analysis, the research team aimed to determine whether cognitive processing speed at study start affected this benefit. The investigators used the Symbol Digit Modalities Test (SDMT), the gold standard measure of cognitive processing speed, with “sustained” change defined as a 4-point or greater change on all follow-up assessments conducted at six-month intervals.
A total of 1,099 patients received Mayzent, while 546 were given placebo. All patients were analyzed, regardless of having cognitive impairment at baseline.
Results showed that the proportion of patients with sustained meaningful improvement in SDMT was greater for Mayzent than for placebo groups, in patients with or without cognitive impairment at the study’s start. However, statistical significance was reached only by those without pre-study impairment, suggesting that patients treated earlier in their disease course and with less cognitive impairment benefited most from the treatment.
“The proportion of patients with sustained improvement in SDMT was most pronounced and significantly greater among Mayzent-versus placebo-treated patients in those patients with no cognitive impairment or patients with relapses,” Benedict said.
The data further showed that treatment with Mayzent was associated with a significantly lower proportion of sustained deterioration in patients with or without cognitive impairment.
However, Mayzent treatment was not associated with significant differences in tests assessing memory, namely the Brief Visuospatial Memory Test-Revised (BVMT-R).
Overall, the results demonstrated that Mayzent treatment “had a significant benefit on processing speed (as measured by SDMT), a key cognitive domain affected by MS,” Benedict said. He also emphasized that “in patients with greater cognitive impairment, Mayzent significantly reduced/prevented further deterioration.”
According to Benedict, “the earlier treatment is initiated, the better the neuropsychological outcome,” ultimately helping patients maintain their independence longer.
In a Novartis press release about these data, Benedict noted: “We are delighted to see Mayzent may protect against cognitive decline, as preserving cognitive function is a crucial aim of disease-modifying MS treatments.”
Danny Bar-Zohar, MD, global head of neuroscience development at Novartis, added: “With Mayzent, we finally have a therapy with proven efficacy in SPMS. The significant effects on cognitive impairment presented at AAN continue to build on the evidence that Mayzent can delay disability progression and positively impact patients’ lives.”
Of note, three of the researchers involved in the study results presented at AAN are affiliated with Novartis.