Treatment with Mayzent (siponimod) led to significant improvement in cognitive processing speed in patients with secondary progressive multiple sclerosis (SPMS), according to updated results of a Phase 3 trial.
Novartis’ findings, presented at the European Academy of Neurology (EAN) congress that ran June 29–July 2 in Oslo, also showed that baseline blood neurofilament light chain (NfL) levels may be a biomarker for SPMS, as they can predict cognitive impairment and disability worsening in this patient population.
The research into Mayzent’s cognitive benefits was disclosed at EAN in a presentation titled “Siponimod Improves Cognitive Processing Speed in Patients with SPMS: Results from Phase 3 EXPAND Study.” It was conducted in participants of the Novartis-funded EXPAND trial (NCT01665144).
Cognitive processing speed was assessed using the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Of note, a four-point change in the SDMT score is considered clinically meaningful. The Brief Visuospatial Memory Test-Revised (BVMTR) was used to evaluate visual/spatial memory.
A total of 1,645 patients — 1,099 on Mayzent, and 546 on a placebo — underwent the three assessments at six-month intervals.
As assessed with the SDMT, SPMS patients on Mayzent in comparison with placebo experienced a 28.6% reduction in the risk of three-point confirmed cognitive worsening and 21.3% lower risk of four-point confirmed worsening.
Results at 24 months showed better scores in up to 40.8% of patients on Mayzent (considering a four-point improvement), compared to up to 30.2% of those on placebo. Change from baseline (study’s start) levels also favored Mayzent.
Results of the PASAT and BVMTR were similar between the two groups.
SPMS patients with relapses within two years of baseline showed improvements in both their SDMT and PASAT scores, while those without relapses had significant changes only in their SDMT scores.
Mayzent “demonstrated a significant and clinically meaningful positive effect on [cognitive processing speed] as measured by SDMT in SPMS patients with/without relapses,” the team wrote.
Similar benefits regardless of cognitive impairment at the study’s start had also been reported at the 2019 American Academy of Neurology (AAN) Annual Meeting. Researchers had also found a lesser risk of sustained cognitive deterioration with Mayzent use, as well as greater improvements if treatment is started early.
Noting that Mayzent’s approval for active SPMS patients in the U.S was based on the typical SPMS patient population studied in EXPAND, Norman Putzki, Novartis’ global program head, neuroscience, said in a press release: “Mayzent can prevent cognitive decline, a fear of many MS patients, as cognitive decline can considerably affect the social and professional lives of these patients and their families.”
Other Novartis work in MS presented at EAN included the latest findings on the self-administered therapy ofatumumab, in development for relapsing forms of MS. Ofatumumab is an antibody targeting a protein called CD20, found on the surface of immune B-cells, which are involved in MS development.
Ofatumumab is approved in the U.S. under the trade name Arzerra for people with chronic lymphocytic leukemia. It is marketed and developed by Genmab, under a development and commercialization agreement with Novartis.