EXPAND shows oral siponimod (BAF312) is the first potential therapy to meaningfully delay disability progression in typical secondary progressive MS (SPMS) patients
Results demonstrate siponimod also had beneficial effects on clinical relapses and MRI disease activity, including brain volume loss (brain shrinkage)
Novartis plans to file siponimod for US approval in SPMS in early 2018. Filing for EU approval planned for later in 2018, pending scientific consultation with EMA
Basel, March 23, 2018 - Novartis today announced 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 significant reductions in the risk of three- (primary endpoint) and six-month confirmed disability progression with siponimod versus placebo and favorable outcomes in other relevant measures of MS disease activity. If approved, siponimod would be the first disease-modifying therapy to delay disability progression in typical SPMS patients, including many who had reached a non-relapsing stage and high level of disability.
SPMS is a form of MS that leads to progressive, irreversible 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,. There is a high unmet medical need for new treatments that are safe and effective for patients with SPMS.
"Today's published, full EXPAND results show that Siponimod can delay disability progression in typical established SPMS patients, where other approaches tested so far have been unsuccessful," said Professor Ludwig Kappos, University Hospital Basel and Principal Investigator of EXPAND. "These data are all the more impressive when considering that the majority of patients already had advanced disability when starting treatment in EXPAND."
- Siponimod is an oral selective modulator of sphingosine-1-phosphate (S1P) receptor subtypes one and five (S1P1 and S1P5),. Full data from EXPAND show that Siponimod reduced the risk of three-month confirmed disability progression by a statistically significant 21% versus placebo (p=0.013; primary endpoint); efficacy was consistent across many pre-defined sub groups. Other clinically relevant endpoint data show that Siponimod, when compared to placebo:
- Reduced the risk of six-month confirmed disability progression by 26% (p=0.0058)
- Slowed the rate of brain volume loss by 23% (relative difference; mean across 12 and 24 months, p=0.0002),
- Limited the increase of T2 lesion volume by approximately 80% (mean over 12 and 24 months, p<0.0001),
- Reduced annualized relapse rate (ARR) by 55% (p<0.0001)
- Did not show a significant difference in the Timed 25-Foot Walk test and MS Walking Scale
- Demonstrated a safety profile that was overall consistent with the known effects of S1P receptor modulation
"Novartis is dedicated to advancing MS research and pioneering solutions for people living with SPMS - a complex, debilitating disease," said Danny Bar-Zohar, Global Head, Neuroscience Development for Novartis. "The pivotal EXPAND data provides patients, and the medical community alike, with hope that a much needed, safe and effective treatment option is on the horizon for SPMS, for which treatment options are scarce. We look forward to continuing to work with regulatory agencies to make Siponimod available for these patients as fast as possible."