Starting Mayzent Early of Greater Benefit in SPMS, 5-Year Trial Data Show

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by Marisa Wexler MS |

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People with secondary progressive multiple sclerosis (SPMS) who began treatment with Mayzent early and continued its use for years are less likely to experience disability progression than those starting the medication later in their disease course, five-year data from the EXPAND study suggest.

Data from this same Phase 3 clinical trial further suggest that Mayzent can help preserve important tissues in the brain, delaying physical disability and slowing cognitive decline.

The findings were published in a supplementary issue of the journal Neurology following the cancellation of the 2020 American Academy of Neurology Annual Meeting due to the COVID-19 pandemic.

Mayzent (siponimod), developed by Novartis, is approved to treat active SPMS in both the United States and Europe. The oral therapy belongs to a class of medications called S1P receptor modulators. These work by ‘trapping’ immune cells in lymph nodes (immunological structures), which can limit the inflammation that causes nervous system damage in MS.

The Phase 3 EXPAND clinical trial (NCT01665144) is evaluating the safety and efficacy of Mayzent in people with SPMS. In the first part of this Novartis-sponsored study, participants were given either Mayzent or a placebo tablet for about three years. Results from this core part of the study, released in 2017, showed that Mayzent significantly slowed disability progression and cognitive decline compared to the placebo.

In its second part, 1,224 people continuing with the study entered an open-label extension phase, in which all were given the active treatment. New data cover this part of the trial.

In one abstract, “Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis Up to 5 Years,” researchers compared disability progression patterns between individuals who switched from placebo to Mayzent in the extension with those getting this treatment since EXPAND’s start. This comparison was to ascertain whether there were significant differences when treatment was started years earlier.

The analysis’ data covered up to five years of follow-up.

Patients given Mayzent at the start had significantly lower average yearly relapse rates compared to those who switched — 0.054 versus 0.097 annual relapses, a decrease of 52%, researchers reported. Those first given Mayzent rather than placebo were also significantly less likely to experience disability progression, and they were 23% less likely to show worsening on the Symbol Digit Modalities Test (a measurement of cognitive impairment).

The benefits seen with early Mayzent treatment were “sustained for up to 5 years, suggesting a continuous effect of siponimod, and underlining the advantages of early treatment initiation,” the researchers wrote.

“These data highlight the critical importance of early treatment intervention with a disease-modifying treatment, such as Mayzent, to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” Bruce Cree, MD, PhD, professor at the University of California, San Francisco, and the abstract’s lead author, said in a Novartis press release.

“It’s never too early to stay ahead of progression in multiple sclerosis, since the early identification of physical and cognitive changes — even subtle ones — can indicate MS disease progression and therefore allow for timely intervention,” Cree added.

EXPAND’s open-label extension will continue for a total of seven years; the trial is due to end in March 2024.

In another abstract, titled “Siponimod Reduces Grey Matter Atrophy in Patients with Secondary Progressive Multiple Sclerosis: Subgroup Analyses from the EXPAND Study,” researchers examined brain imaging data from 1,560 participants in the core phase of the EXPAND trial. Researchers specifically looked at changes in gray matter.

The brain can be divided into two types of tissue: gray matter and white matter. Gray matter contains the majority of neurons in the brain, and loss of this tissue (termed gray matter atrophy) has been linked with disability progression in MS.

“Grey matter atrophy is more pronounced in progressive forms of multiple sclerosis and is associated with long-term irreversible disability accumulation,” the researchers wrote.

After one and two years of treatment, results showed that gray matter atrophy was significantly lesser in people treated with Mayzent than in those given a placebo. The magnitude of the reduction varied from 48% to 116% among different subgroups of patients (defined by age, disease duration, disability scores, cognitive scores, and pretreatment disease activity), but all were statistically significant.

Atrophy in the thalamus — a gray matter-dense brain region important for sensorimotor functions —  also lessened with Mayzent treatment. The magnitude of this reduction varied from 30% to 68%, and it was statistically significant for all patient subgroups except those with disease duration longer than 15 years.

“Siponimod consistently reduced cGM [cortical grey matter] and thalamic atrophy across SPMS subgroups, including those with less active and more advanced disease. Combined with other analyses, these effects might potentially translate into a favorable impact on long-term clinical outcome including disability progression and cognitive decline,” the researchers wrote.

Importantly, previous data from EXPAND suggested that treatment with Mayzent can reduce the risk of people with SPMS becoming dependent on a wheelchair.

These “data continue to show that Mayzent has the ability to help patients maintain independence for longer through its long-term effect on delaying progression and cognitive impairment,” said Norman Putzki, MD, global head of development neuroscience at Novartis.

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