Experimental Medications: NEW S1P Receptor Modulators
- Oral medication studied at several doses
- Being studied in SPMS
Siponimod is a drug with a mechanism of action similar to Gilenya. Like Gilenya, it works at the S1P receptor family to block the movement of lymph cells from lymph nodes, however, siponimod appears to interact with less of the receptors than Gilenya does – with its primary actions at the S1P1 and the S1P5 receptors. Siponimod has a relatively short half-life compared to Gilenya, which means that the drug does not stay in the body as long. Researchers hope that these small differences will minimize cardiac issues.
In RRMS, results from a Phase II dose-finding study of siponimod were reported in 2012. The trial had a complex design, with the primary goal to determine the most appropriate dose to carry forward into future trials. Approximately 300 people participated in the study. At six months, the proportion of relapse-free patients was 84 percent for the 10 mg group, 92 percent for the 2 mg group, and 77 percent for the 0.5 mg group, as compared to 72 percent in the placebo group. After six months, the ARR (annualized relapse rate) was lower for the individuals who were taking one of the three higher doses. Additionally, regarding MRI parameters, the 2 mg dose reached statistical significance versus placebo, with a reduction in active lesions of approximately 80 percent.
Some of the most exciting news in MS research from the last year surrounded the announcement of the results of EXPAND, a Phase III trial of siponimod in SPMS.18 The trial randomized 1,651 patients with SPMS to siponimod versus placebo in a 2:1 ratio (two times as many patients were given siponimod versus placebo). The primary endpoint of the EXPAND trial was time to three-month confirmed disability progression (CDP). CDP was met when a participant developed an increase in his or her disability that is confirmed by a repeat exam three-months later.
This trial was able to show a small, yet statistically significant, decrease in three-month CDP of 21 percent in those on the study drug compared to those on placebo. Participants in the siponimod arm also showed 23.4 percent slower decrease in their brain volume as compared to placebo. However, no difference was observed between the two groups in changes in the timed 25-foot-walk. Relapses were decreased in the group taking siponimod. Overall, patients tolerated the drug well, though more serious adverse events and infections occurred in the siponimod group.