Siponimod Slows Progression of MS Disability, Phase 3 Clinical Trial Shows

Siponimod slows the progression of multiple sclerosis patients’ disability, a Phase 3 clinical trial indicates.

The therapy reduced the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS) by 21 percent over three months, researchers said. At six months, the reduction was 26 percent, they said.

Researchers presented the findings of the Phase 3 EXPAND study (NCT01665144) in two poster sessions at the American Academy of Neurology’s annual meeting in Boston, which ended today.

Siponimod acts on two types of a protein called the sphingosine-1-phosphate receptor that is present on immune cells known as immune lymphocytes. By binding to the proteins, siponimod keeps lymphocytes in lymph tissue rather than entering the brain and spinal cord. This reduces inflammation. The proteins are also found on brain cells believed to contribute to SPMS.

“Experimental animal and in vitro [laboratory] studies also suggest that siponimod, besides its peripheral anti-inflammatory effects, may promote repair mechanisms in the central nervous system mediated by astrocytes and oligodendrocytes,” Dr. Ludwig Kappos, the author of the study, said in a news release.

The EXPAND trial, which covered 1,651 SPMS patients from 31 countries, looked at whether 2 mg a day of siponimod would lower the risk of disability progression, compared with a placebo. All of the patients had a moderate disability level, ranging from 3.0 to 6.5 on the Expanded Disability Status Scale (EDSS).

One poster presentation was titled “Efficacy Of Siponimod In Secondary Progressive Multiple Sclerosis: Results Of The Phase 3 Study.” It showed that, at three months, siponimod decreased by 21 percent the risk that patients’ disability would progress one EDSS step. This met the study’s primary goal. Siponimod decreased the risk of disease progression at six months by 26 percent.

The yearly relapse rate of those who took siponimod fell 55.5 percent, according to the study. The therapy also decreased the number of lesions in the T1 area of the brain by 86.6 percent and the number in the T2 region by 81 percent. The results were considered significant.

Siponimod did not significantly improve the time before patients’ condition worsened. The yardstick researchers used for this conclusion was the Timed 25-Foot Walk Test, which assesses mobility and leg function performance.

The other poster presentation, “Safety And Tolerability Of Siponimod In Patients With Secondary Progressive Multiple Sclerosis,” showed that siponimod was well-tolerated, with expected side effects.

“We observed an overall incidence of adverse events and severe adverse events comparable to placebo,” Kappo said. “Incidence as well as severity of infections was comparable between treatment groups, while the incidence of heart rate and conduction adverse events, macular edema, and herpes zoster was higher under siponimod.”

Overall, the EXPAND study supports the use of siponimod as an SPMS treatment, the researchers siad.

“The fact that this study was a success is a big deal,” said Dr. Lauren B. Krupp, an MS expert. “The difficulty with SPMS is that it usually involves slightly older patients who are at increased risk for complications. So, we’ll have to see if complications show up as the drug is used with patients over longer periods of time and over multiple years. In the meanwhile, the results are very exciting. It’s a breakthrough moment.”