Novartis‘ siponimod (BAF312) can reduce blood levels of a biomarker of nerve cell damage in patients with secondary progressive multiple sclerosis (SPMS), a Phase 3 clinical trial shows.
Researchers will present the latest results of the ongoing trial at the 2018 annual meeting of the American Academy of Neurology in Los Angeles, April 21-27. The presentation will be titled “Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.”
Previous studies have shown that blood levels of a protein called neurofilament light chain (NfL) can provide a reliable picture of the activity of both the relapsing-remitting and progressive forms of multiple sclerosis. It could even be a tool to monitor the disease, instead of magnetic resonance imaging scans of the brain. That’s because the protein’s levels reflect nerve cell damage.
In the phase 3 EXPAND trial (NCT01665144), researchers looked at siponimod’s ability to lower levels of NfL in the blood of 1,452 SPMS patients. Participants received either 2 mg of oral siponimod or a placebo once a day.
The 525 patients who took siponimod for more than 21 months had a 5.7 percent reduction in NfL levels, whereas those in the placebo group had a 9.2 percent increase.
This significant change applied to both the 212 patients who had relapses in the two years before the study began and in the 312 who had no relapses. The blood levels of NfL in the previous-relapses group fell by 10.5 percent with siponimod, versus a 7.1 percent increase in the placebo group. The figures in the no-relapses category were a 2.5 percent reduction in the siponimod group, compared with a 10.7 percent increase in the placebo group.
Collectively, the results suggested that siponimod can reduce SPMS activity, as measured by blood NfL levels. Researchers said additional studies were needed to address the “dynamics and relevance of NfL serum levels in progressive disease,” however.
Siponimod inhibits the activity of two sphingosine-1-phosphate receptors on the surface of immune cells. This prevents the cells from traveling to the brain and spinal cord, where they can do damage and trigger MS. The findings indicated that siponimod indirectly reduces the inflammatory process that contributes to SPMS, researchers said.
The latest EXPAND results showed that siponimod can reduce the risk of disability progression in SPMS patients. Also, it significantly slowed brain shrinkage compared with a placebo, and reduced annual relapse rates.
Novartis plans to submit a marketing application for siponimod as a SPMS disease-modifying therapy with the U.S. Food and Drug Administration and the European Medicines Agency soon.