Novartis’ investigational oral treatment siponimod (BAF312) reduces the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS), a new analysis of Phase 3 trial results show.
Using what the company describes as more accurate methods to assess siponimod effect’s on progression risk, necessary because the potential treatment reduces relapse rates, this new data add to recently reported results. Specifically, the findings show that siponimod’s clinical benefits in slowing progression are largely independent of relapses.
Treatment was also reported to improve patients’ cognitive processing speed, defined as the time taken to perform a mental task. The ability to quickly process information can be severely affected in SPMS patients.
This data are being presented at the 2018 American Academy of Neurology (AAN) Annual Meeting in the study, “Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Non-relapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase III EXPAND Study.” AAN ends Friday, April 27, in Los Angeles.
The double-blind EXPAND trial (NCT01665144) is assessing siponimod’s efficacy and safety in SPMS patients. The study included 1,651 patients in 31 countries, with a mean age of 48 and living with MS for nearly 17 years. Participants had scores on the Expanded Disability Status Scale (EDSS) between 3.0 and 6.5, which corresponds to moderate to severe disability.
Patients were randomly assigned in the study’s double-blind part to either 2 mg siponimod or placebo once daily. They have the option of continuing siponimod treatment in the study’s open-label long-term extension.
This analysis showed that siponimod in non-relapsing patients lowered disability progression by 14–20% at three months and by 29–33% at six months compared to placebo, indicating that the treatment’s effect on disability progression was disassociated from relapses.
“Siponimod’s beneficial effect on preventing disability progression, independent from its reduction in relapse frequency, demonstrates that patients with secondary progressive MS could benefit from this treatment,” Bruce Cree, MD, PhD, a member of the study’s steering committee and a professor at University of California, San Francisco, said in a press release.
“This is very exciting because many people diagnosed with relapsing-remitting MS, the most common form of the disease, will ultimately transition to SPMS, where without effective new therapies, they experience gradual worsening of disability despite infrequent relapses,” Cree added.
Changes in cognitive processing speed were evaluated using the Symbol Digit Modalities Test (SDMT), which has established clinical validity, and other tools. Siponimod-treated patients showed improvements in processing speed from baseline (study start) through month 24. These benefits were seen both in patients who had relapses within two years of baseline and those who did not. No changes in memory were observed.
“A decline in the ability to rapidly process information affects more than half of MS patients and is more severe in [SPMS] than relapsing-remitting MS. These data show that siponimod could have a meaningful impact on these patients’ daily lives,” said Danny Bar-Zohar, global head of neuroscience development at Novartis.
“Furthermore, the advanced models used in the new analyses help us to better understand the relationship between relapses and disability and the effect of siponimod on these parameters. We are encouraged by these latest findings, which further solidify the clinical evidence for siponimod as a potential new, much needed treatment option for SPMS,” he added.
Prior results also showed that siponimod slowed patients’ brain shrinkage by 23 percent, and decreased their annualized relapse rate by 55 percent.
At AAN 2018, Novartis also presented EXPAND trial data showing that the potential treatment reduces blood levels of a biomarker — a protein called neurofilament light chain — of nerve cell damage.
Novartis is planning to soon file a marketing application, requesting siponimod approval, with the U.S. Food and Drug Administration. A similar filing in Europe is expected later this year.
Siponimod selectively binds to two sphingosine-1-phosphate receptors in lymphocytes, a type of immune cell. The binding prevents lymphocytes from entering the brain and spinal cord, easing inflammation in SPMS patients. Siponimod also enters the central nervous system, where it binds to specific cell types to potentially slow a loss of neurological function in patients.
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