Novartis' Siponimod significantly improved outcomes in PhIII data published in Lancet

Novartis announced Thursday that the full results from the Phase III EXPAND study of oral, once-daily siponimod (BAF312) in secondary progressive multiple sclerosis (SPMS) were published in the peer-reviewed journal The Lancet. These pivotal results show siponimod significantly reduced the risk of three-month confirmed disability progression versus placebo (primary endpoint). Siponimod also meaningfully delayed the risk of six-month confirmed disability progression and demonstrated favorable outcomes in other relevant measures of multiple sclerosis (MS) disease activity. If approved, siponimod would be the first disease-modifying therapy to delay disability progression in a large trial of typical SPMS patients, including many who had reached a non-relapsing stage and high level of disability.

In October, results from the EXPAND trial was shared at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris. One key finding was that siponimod reduced the number of patients’ gadolinium-enhancing inflammatory lesions by 86.6 percent after a year. After two years, the average reduction was even better — 91.1 percent. Gadolinium-enhancing lesions indicate that inflammation is ongoing.

Another important finding was that siponimod-treated patients had experienced 39 percent less brain volume loss than placebo-treated patients after a year.

SPMS is a form of MS that is associated with progressive, irreversible physical and cognitive disability, largely independent of relapses. Patients transition to SPMS after an initial phase of relapsing-remitting MS (RRMS), the most commonly diagnosed type of MS. Most people with relapsing-remitting MS eventually get secondary progressive MS. The relapses and remissions that used to come and go change into symptoms that steadily get worse. The shift typically begins 15 to 20 years after the initial diagnosis of MS.

Siponimod is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs.

Other clinically relevant endpoint data from the EXPAND trial showed that siponimod, when compared to placebo:

• Did not show a significant difference in the Timed 25-Foot Walk test, the first key secondary endpoint, and the MS Walking Scale

• Limited the increase of T2 lesion volume by approximately 80%, measured by volume change from baseline (mean over 12 and 24 months, p<0.0001), the second key secondary endpoint

• Reduced the risk of six-month confirmed disability progression by 26% (p=0.0058)

• Reduced annualized relapse rate (ARR) by 55% (p<0.0001)

• Slowed the rate of brain volume loss by 23% (relative difference; mean across 12 and 24 months, p=0.0002)

• Demonstrated a safety profile which was overall consistent with the known effects of S1P receptor modulation

Novartis plans to file for regulatory approval of siponimod for SPMS with the FDA in early 2018. MS affects approximately 400,000 people in the US and 2.5 million worldwide.