Siponimod Delays Disability, Benefits Cognition, Analysis Shows

September 12, 2020

Post hoc data from 2 late-stage studies about siponimod, sold as Mayzent by Novartis, illustrated improved cognitive processing speed and delayed time to disability in multiple sclerosis.

When used early in multiple sclerosis, siponimod (Mayzent) delays disability progression and show benefits in cognitive performance in patients with secondary progressive multiple sclerosis (SPMS), according to Novartis. The benefits were sustained for up to 5 years.

The data were released during MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting taking place September 11–13, 2020.

Siponimod is an oral selective sphingosine 1-phosphate (S1P) receptor modulator that may directly prevent degeneration of nerve fibers. It was approved in 2019 and was the first SPMS treatment to be approved in 15 years; it is also indicated for relapsing multiple sclerosis (RMS).

One analysis assessed the long-term efficacy and safety of siponimod in patients with active SPMS (aSPMS) from the pivotal EXPAND study.1 Patients with aSPMS are had a relapse 2 years prior to screening and/or had a lesion at baseline. End points were 6-month confirmed disability progression (6mCDP) and 6-month confirmed cognitive worsening (6mCCW).

Of the 1651 patients randomized in the core group, 1224 entered the extension. Of the 779 patients with aSPMS from the core group, 516 had been taking the drug continuously, and 263 had switched from placebo to siponimod in the extension; 582 entered this part of the extension.

The risk of 6mCDP was reduced by 29% (HR, 0.71; 95% CI, 0.57-0.90; P = .0044) for the continuous versus switch group, translating to about a 70% delay in time to 6mCDP across the 25th to 40th percentile.

Median time to 6mCDP was 48 months for the switch group, but was not reached for the continuous group.

The risk of 6mCCW for the continuous versus the switch group was reduced by 33% (HR, 0.67; 95% CI, 0.53-0.86; P = .0018), corresponding to about a 70% delay in time to 6mCCW across the 25th to 30th percentile.

Median time to 6mCCW (55.5 months) was reached only for the switch group.

In addition, a significant reduction in annualized relapse rate (ARR) for the continuous versus switch groups was observed in patients with (0.08 vs 0.12; P = .0023) or without active disease (0.03 vs 0.08; P < .0001).

Another poster examined the effect of siponomid on cognitive processing speed in patients with SPMS with both active and non-active disease by measuring improvement in the Symbol Digit Modalities Test (SDMT).2

Researchers were looking for a change in SDMT score by 4 points or more from baseline to month 24, as well as the proportion of patients with worsened, stable and improved SDMT scores at month 24.

Results showed that the drug “showed significant benefits in cognitive processing speed as measured by SMDT change from baseline in patients with both active and non-active SPMS,” according to a recorded presentation.

Change in SDMT (95% CI) versus placebo from baseline to month 24 in patients with aSPMS and non-active SPMS was 2.34 (0.66-4.02) and 2.44 (0.67-4.22; P <.01 for both, respectively).

In the aSPMS group, a lower proportion of patients worsened (27.3% vs 38.2%, P = .002) and a higher proportion of patients improved (34.1% vs 22.9%, P = .001) on SDMT versus placebo.

A similar but non-significant trend was seen in patients with non-active SPMS.

“The data presented today reinforces that through its beneficial effects on cognitive performance and delaying disability progression, and as an appropriate option for patients to safely switch to/from other treatments, Mayzent offers hope for people looking to achieve this important goal,” Norman Putzki, MD, Global Head of Development, Neuroscience, said in a statement.

References

  1. Giovannoni G, Kappos L, Fox RJ, et al. Sustained reduction of disability and cognitive decline with long-term siponimod treatment in patients with active SPMS: EXPAND data up to 5 years Presented at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11–13, 2020. Poster PO238.
  2. Penner IK, Giovannoni G, Cree BAC, et al. Effect of siponimod on cognitive processing speed in SPMS patients with active and non-active disease. Presented at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11–13, 2020. Poster PO806.