These findings further corroborate prior trial data demonstrating that Mayzent use delays disability progression and cognitive decline in SPMS patients.
The results were disclosed at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which ran Sept. 11-13 in Stockholm, Sweden. The presentation, titled “Siponimod delays the time to wheelchair in patients with SPMS: results from the EXPAND study,” was given by Patrick Vermersch, MD, PhD, neurologist and researcher at the University of Lille, France.
SPMS is characterized by steadily worsening disease, including the progressive loss of walking ability.
“Worsening of ambulation is one of the key features of SPMS, which eventually leads to increased dependence on a wheelchair in a large number of patients,” Vermersch said.
Novartis‘ Mayzent is a sphingosine-1-phosphate (S1P) receptor modulator for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active SPMS.
The FDA’s decision was based, in part, on data from the EXPAND Phase 3 clinical trial (NCT01665144). That data showed that SMPS patients taking oral Mayzent experienced a decrease in disability progression and in cognitive decline.
The trial included a total 1,651 people with SPMS, with moderate-to-severe disability, whose condition had deteriorated over the two years prior to the study’s start. Participants, recruited across 31 countries, were randomly selected to receive 2 mg of Mayzent orally or a placebo, once per day, and were followed for up to three years. An open-label extension study for up to 10 years is ongoing.
In this new analysis, researchers used the trial’s data to address whether Mayzent use could slow down disability to the point that it would prevent patients from progressing on the Expanded Disability Status Scale (EDSS), which quantifies disability in MS. The goal was to prevent individuals with SPMS from progressing to an EDSS score of 7 or higher — meaning, to prevent them from essentially becoming wheelchair-bound. This analysis focused on data until the last assessment in the core part of the EXPAND trial (up to 3 years).
Researchers measured the time it took for patients in two different populations to reach this high level of disability. One was a high-risk group who entered the study with an EDSS score of 6.5. Among them, 293 received Mayzent, while 119 were assigned placebo. The other, larger group, was the overall EXPAND population. In that group, 1,099 took Mayzent, while 546 received placebo.
The chances of progressing through worse disease states were estimated, and results were extrapolated to the overall population to calculate the median time to reach a disability value of 7 or higher. The researchers said this data extrapolation was based on the assumption that the treatment effect was preserved over time.
Results showed that, compared with placebo, fewer patients at greater risk of worsening — those with an EDSS score of 6.5 — in the Mayzent group became dependent on a wheelchair. Specifically, the results showed 19.2% of the Mayzent group becoming wheelchair dependent versus 26.1% in the placebo group. This translated into Mayzent treatment leading to a 37.3% reduction in risk.
In the overall study population, Mayzent reduced by 31% the risk of reaching EDSS 7 or higher — and therefore becoming unable to walk, and restricted to a wheelchair — compared with placebo. However, this result was “not really significant,” Vermersch said. He said the results suggested that “the population at-risk was ‘diluted’ in the overall population, with less risk of many patients … reaching EDSS 7 within this period of time.”
Assuming Mayzent’s effect is stable over time, and extrapolating the prior estimates to the overall study population, the medicine was predicted to prolong the median time patients lived until becoming wheelchair-bound by 4.3 years. The median time was 16.3 years for Mayzent-treated patients versus 12.0 years for the placebo group.
“Results from this analysis translate to potential long-term benefit beyond the core part of the EXPAND trial,” Vermersch said.
“Under assumptions of the model that treatment effect is preserved, siponimod [Mayzent] delayed the median time to wheelchair dependence by 4.3 years in the overall population, compared with placebo” treatment, Vermersch concluded.
According to the researcher, the data “further support the clinical relevance of the effect of siponimod on delaying disability progression in patients with SPMS.”
Novartis said its ultimate goal is to “reimagine” MS treatment.
“Delaying disability progression and slowing declining cognitive function can mean maintaining independence for longer and matters a lot to people living with MS and physicians,” Norman Putzki, MD, PhD, global program head at Novartis, said in a press release.
“We are excited that these data once again underline the true value of Mayzent,” Putzki said.
“Mayzent expands possibilities for patients with MS, resulting in fewer relapses, reduced lesion volume increase, improved cognitive processing speed, reduced grey matter volume loss, and delayed time to wheelchair,” he concluded.