Novartis today announced new analyses from the Phase III EXPAND study of oral, once-daily siponimod (BAF312) in patients with secondary progressive multiple sclerosis (SPMS). In pre-specified statistical analyses, treatment with siponimod consistently reduced the risk of confirmed disability progression in SPMS patients, with and without relapses[1]. In addition, new post-hoc analyses using more accurate methods to estimate the treatment effect on disability progression, now substantiate that the risk reduction with siponimod is largely disassociated from relapses. Siponimod also showed a significant benefit on cognitive processing speed, the key cognitive function impacted by MS, which frequently deteriorates in people with the disease[2]. These results are being presented at the 70th American Academy of Neurology (AAN) Annual Meeting, in Los Angeles, USA, April 21-27, 2018.
As previously reported for the overall study population, treatment with siponimod resulted in a statistically significant risk reduction in disability progression sustained for three- and six-months[4]. The new EXPAND study analyses, using a more advanced model-based approach, show an estimated risk reduction for disability progression, sustained at three-months that ranged from 14-20% compared to placebo (calculated by principal stratum analysis) for non-relapsing patients. For disability sustained at six-months, estimated risk reduction was even greater, spanning from 29-33%. Other complementary statistical approaches[1] assessing the effect of siponimod on disability progression disassociated from relapses showed consistent results.
“Siponimod’s beneficial effect on preventing disability progression, independent from its reduction in relapse frequency, demonstrates that patients with secondary progressive MS could benefit from this treatment,” said study steering committee member Bruce Cree, MD, PhD, MAS, Clinical Research Director and Associate Professor, University of California, San Francisco, School of Medicine. “This is very exciting because many people diagnosed with relapsing-remitting MS, the most common form of the disease, will ultimately transition to SPMS, where without effective new therapies, they experience gradual worsening of disability despite infrequent relapses.”
In pre-specified and post hoc analyses, siponimod’s effect on cognitive processing speed was evaluated, as measured by the Symbol Digit Modalities Test (SDMT). SDMT is the only cognitive test with established clinical relevance of change in MS and is widely accepted by patients and physicians[5]. Other tests included the Paced Auditory Serial Addition Test (PASAT, assessing cognitive processing speed) and the Brief Visuospatial Memory Test-Revised (BVMT-R, assessing memory)[6],[7]. From baseline to month 24, treatment with siponimod showed a significant benefit on cognitive processing speed, compared to placebo, for all patients (SDMT, p=0.0004), and also in those who had relapses within two years before starting the trial (SDMT p=0.0151; PASAT p=0.0275) and those who did not (SDMT p=0.0099; PASAT not statistically significant)[2]. Treatment with siponimod did not result in significant differences in memory (BVMT-R)[2].
“A decline in the ability to rapidly process information affects more than half of MS patients and is more severe in secondary progressive MS than relapsing-remitting MS. These data show that siponimod could have a meaningful impact on these patients’ daily lives,” said Danny Bar-Zohar, Global Head Neuroscience Development, Novartis. “Furthermore, the advanced models used in the new analyses help us to better understand the relationship between relapses and disability and the effect of siponimod on these parameters. We are encouraged by these latest findings, which further solidify the clinical evidence for siponimod as a potential new, much needed treatment option for SPMS.”
Novartis has initiated the submission of siponimod for US approval in SPMS in the first half of 2018. Filing for EU approval is planned to follow later in 2018.
