Synonyms: BAF-312 | BAF312 | compound 32 [PMID: 24900670] | Mayzent®
siponimod is an approved drug (FDA (2019), EMA (2020))
Compound class:
Synthetic organic
Comment: Pharmacologically, siponimod (BAF312) is a selective sphingosine-1-phosphate (S1P) receptor agonist, with some selectivity for the S1P1 and S1P5 receptor isoforms [8]. It is an orally active drug. Siponimod was developed by Novartis for secondary progressive multiple sclerosis (SPMS), originally as a back-up compound for fingolimod. Compared to fingolimod it has more favourable pharmacokinetics.
Novartis announced positive results from their Phase 3 EXPAND study (BAF312 versus placebo) in SPMS (August 2016- link to announcement here). The SIPR signalling pathway is important in autoimmune biology. ![]() Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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No information available. |
Summary of Clinical Use ![]() |
Siponimod was granted FDA approval in March 2019, for the treatment of relapsing forms of multiple sclerosis (secondary progressive multiple sclerosis with active disease, relapsing remitting multiple sclerosis and clinically isolated syndrome), following positive outcomes from the Phase 3 EXPAND trial NCT01665144 [5]. EMA approval followed in January 2020. Click here to link to ClinicalTrials.gov's full list of siponimod (BAF312) trials. |
Mechanism Of Action and Pharmacodynamic Effects ![]() |
Tha main aim of treatment with siponimod is to delay disability progression and preserving cognition in multiple sclerosis (MS) patients. The sphingosine 1-phosphate receptor (S1PR) pathway is a validated drug target for multiple sclerosis (MS) [10], with the S1P1,3-5-R pan-agonist fingolimod already approved as the first oral drug for the treatment of relapsing-remitting MS. S1PR agonists decrease the number of circulating peripheral blood lymphocytes [3,6] and subsequently produce an immunosuppressant effect which results in attenuation of demyelination [7] and prevents synaptic neurodegeneration in experimental MS [2] in vitro. As it has a shorter circulating half life compared to fingolimod, siponimod is expected to be less likely to cause induced lymphopenia, one of the most problematic side effects associated with fingolimod therapy. |
Clinical Trials | |||||
Clinical Trial ID | Title | Type | Source | Comment | References |
NCT01665144 | Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND) | Phase 3 Interventional | Novartis | In this trial siponimod reduced the risk of disability progression in patients with SPMS. Its risk profile was similar to that of other S1P modulators. | 5 |