siponimod / Generic mfg. - LARVOL DELTA

Therapeutic targeting of sphingosine-1-phosphate receptor 1 (S1PR1) in angioimmunoblastic T-cell lymphoma. (ASH 2025) - "The molecular landscape of AITL is characterized by frequent genomic alterationsin epigenetic regulators, including TET2, DNMT3A, and IDH2, as well as components of the T-cell receptor(TCR) signaling pathway...This, together with our observation of increased S1PR1 expression in humanRHOA G17V⁺ AITL tumor samples, identifies S1PR1 deregulation as a potentially relevant effector of theoncogenic effects of RHOA G17V in TFH cells.S1P receptor inhibitors, such as fingolimod (FTY720) and next-generation, more selective modulatorssuch as ozanimod, siponimod, and ponesimod, are FDA-approved for the treatment of multiple sclerosisand other autoimmune diseases...These findings definean S1PR1–STAT3 inflammatory loop that promotes survival and dissemination in RHOA G17V-driven AITLand identify this axis as a therapeutically actionable vulnerability.In summary, our preliminary data establish a mechanistic link between oncogenic RHOA signaling andS1PR1-mediated membrane receptor..."

IO biomarker • CNS Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD4 • DNMT3A • IDH2 • IL6 • RHOA • S1PR1 • S1PR5 • TET2 • TNFA

Cerebellar Subregional Atrophy in Relapsing-Remitting Multiple Sclerosis: Stage-dependent Dynamics and Pharmacological Modulation. (PubMed, Brain Res Bull) - "This study demonstrated stage-specific patterns of cerebellar atrophy in RRMS and the heterogeneous, stage-dependent effects of DMTs on posterior cerebellar subregions. Lobules IX and VIIIb emerged as critical loci linking pharmacological modulation with cognitive outcomes. These findings suggest that these regions may serve as potential imaging biomarkers of therapeutic response and prognosis in MS."

Journal • CNS Disorders • Multiple Sclerosis

Selected aspects of epidemiology of multiple sclerosis in Poland: a multicenter pilot study. (PubMed, Neurol Neurochir Pol) - "This study highlights substantial progress in the diagnostic and therapeutic management of MS in Poland over the past 15 years. The widespread implementation of MRI and CSF analysis, alongside significantly improved access to DMTs, has contributed to notably better clinical outcomes. These improvements are reflected in reduced relapse rates, slower disability progression, and a decreased prevalence of secondary progressive MS."

Journal • CNS Disorders • Multiple Sclerosis

Lupin receives USFDA tentative nod for Siponimod tablets (Business Standard) - "The product is a generic equivalent of Novartis Pharmaceuticals Mayzent Tablets and is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease, in adults....According to IQVIA MAT October 2025 data, Siponimod Tablets (reference listed drug Mayzent) recorded annual U.S. sales of USD 195 million."

ANDA • Sales • CNS Disorders • Multiple Sclerosis

Siponimod inhibits disease-associated microglia-T cell interactions in chronic experimental autoimmune encephalomyelitis. (PubMed, Acta Neuropathol Commun) - "Additionally, we observed reduced peripheral T cell numbers in our EAE model, with a pronounced shift to immunosenescent and regulatory T cell subsets, a pattern which we similarly detected in a cohort of SPMS patients following siponimod treatment. These findings indicate that siponimod dampens compartmentalized CNS inflammation by disrupting detrimental interactions between T cells and microglia through a dual central and peripheral mechanism of action."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • IFNG

Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved Disease-Modifying Treatments for Multiple Sclerosis. (PubMed, Eur J Neurol) - "Future proof-of-concept clinical trials investigating remyelinating agents in MS should consider combining outcome measures into composite endpoints. Furthermore, research efforts should be dedicated to novel biomarkers to assess repair mechanisms in MS."

Journal • Review • CNS Disorders • Multiple Sclerosis • Solid Tumor

A real-world retrospective study to assess the effectiveness and safety profile of siponimod in Chinese patients with relapsing forms of multiple sclerosis. (PubMed, BMC Neurol) - "This RW study confirmed favourable benefit-risk profile of siponimod in Chinese patients with RMS."

Journal • Real-world evidence • Retrospective data • CNS Disorders • Multiple Sclerosis

Selective Activation of GPCRs: Molecular Dynamics Shows Siponimod Binds but Fails To Activate S1PR2, Unlike S1PR1. (PubMed, J Chem Inf Model) - "Our findings elucidate molecular determinants of Siponimod's selectivity toward S1PR1 and highlight these residues as potential differentiators for selective modulator design. This study demonstrates how structural and dynamic insights from atomistic simulations aid rational drug design for targets with high homology."

Journal • Cardiovascular • CNS Disorders • Multiple Sclerosis • S1PR1 • S1PR2

Dual Mechanisms of Cognitive Function and Pathological Improvements by the Selective S1PR1/5 Modulator Siponimod in 3xTg-AD Mice. (PubMed, Mol Neurobiol) - "This study demonstrates that Siponimod effectively treats AD through dual mechanisms: reducing neuroinflammation and promoting myelin repair via the S1PR1/5 and PI3K-AKT signaling pathway. These findings suggest Siponimod's potential as a promising therapeutic agent for AD treatment."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation • OLIG2 • S1PR1

Effectiveness and safety of ofatumumab in treatment-naive and oral DMT-switched multiple sclerosis patients: a multicenter observational study in China. (PubMed, Mult Scler Relat Disord) - "This real-world study revealed a significant decrease in disease activity and progression among MS patients treated with ofatumumab, both in treatment-naïve and oral DMTs-switched patients, while maintaining a well-tolerated safety profile."

Journal • Observational data • CNS Disorders • Multiple Sclerosis

Clinical sphingosine 1-phosphate receptor agonists protect oligodendrocytes in the cuprizone demyelination model (Neuroscience 2025) - "Both S1PR1- and S1PR5-selective agonists protected mature oligodendrocytes against cytokine-induced cell death in an in vitro oligodendrocyte model, suggesting that the mechanisms of protection in vivo are more complex.In conclusion, siponimod has direct neuroprotective actions in the CNS. As siponimod but not ozanimod protected against oligodendrocyte loss, it is likely that the protective effects of siponimod in vivo are mediated at least partially through S1PR5."

Clinical • CNS Disorders • S1PR1 • S1PR5

External Reference Pricing (ERP) Availability vs. Reimbursement Timelines in Poland and Other European Countries: The Analysis of EURIPID Database (ISPOR-EU 2025) - "20 MPs (INN, strength, dosage form) with 11 active substances were selected for the analysis: abrocitinib, acalabrutinib, asciminib, avatrombopag, bimekizumab, larotrectinib, pegcetacoplan, siponimod, trastuzumab deruxtecan, tucatinib, zanubrutinib. Shorter time to launch was associated with higher prices of reimbursed MPs and lower availability of ERP information. The EURIPID database served as a useful source of information and a tool for pricing analysis."

Pricing • Reimbursement • US reimbursement

A Study of Kyv-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (ASH 2024) - P1 | "Currently approved treatments include siponimod, an S1P receptor modulator, and ocrelizumab, an anti-CD20 monoclonal antibody...After apheresis and CAR T-cell production, participants will receive standard lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single infusion of KYV-101 at one of two dose levels...The study is expected to complete in 2026. MRS and SG contributed equally to the work"

CAR T-Cell Therapy • CNS Disorders • Multiple Sclerosis

Gastrointestinal Adverse Effects of Sphingosine-1-Phosphate (S1P) Receptor Modulators: A Real-World Pharmacovigilance Study (ACG 2025) - "Out of 26,928 S1P-related reports, 3,535 (13.1%) involved GI AEs. The proportion of GI AEs was highest for ozanimod (17.78%), followed by siponimod (13.02%), fingolimod (10.84%), and ponesimod (9.06%). Serious GI AEs accounted for 58% of cases."

Adverse events • Clinical • Real-world • Real-world evidence • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis

The effect of disease-modifying therapies on brain volume loss and disability accumulation in multiple sclerosis: a systematic review and network meta-analysis. (PubMed, Lancet Reg Health Eur) - "Eight DMTs significantly reduced BVL compared to placebo, including ponesimod (ROM = 0.52; 95%-CI: 0.35-0.77), ofatumumab (ROM = 0.58; 95%-CI: 0.40-0.83), alemtuzumab (ROM = 0.63; 95%-CI: 0.49-0.83), teriflunomide (ROM = 0.71; 95%-CI: 0.52-0.97), ozanimod (ROM = 0.74; 95%-CI: 0.56-0.98), natalizumab (ROM = 0.77; 95%-CI: 0.61-0.96), siponimod (ROM = 0.77; 95%-CI: 0.60-0.98), and fingolimod (ROM = 0.83; 95%-CI: 0.71-0.96)...These findings support BVL as a meaningful treatment target in MS. None."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis

NEW TREATMENTS OF MULTIPLE SCLEROSIS (WCN 2025) - "This teaching course will provide a comprehensive overview of the latest advancements in MS treatment, including B-cell depleting therapies (e.g., ocrelizumab), cladribine, Bruton's tyrosine kinase (BTK) inhibitors, and sphingosine-1-phosphate (S1P) receptor modulators, with a focus on their mechanisms, clinical applications, emerging indications, and safety considerations...BTK inhibitors (e.g., evobrutinib, tolebrutinib), currently in phase III trials, target both peripheral and CNS-resident immune cells, showing promise for progressive MS. S1P receptor modulators (e.g., fingolimod, siponimod) regulate lymphocyte trafficking and are approved for RMS and secondary progressive MS (SPMS)...Additionally, this course will explore smoldering MS pathology, including chronic active lesions and neurodegeneration, and discuss whether emerging therapies, particularly BTK inhibitors, can address progression beyond relapse suppression. Through case discussions and trial data,..."

CNS Disorders

Transitions in SPMS Diagnosis and DMT Use Following Siponimod Reimbursement: Evidence from the Czech ReMuS Registry (2016–2023) (ECTRIMS 2025) - "Between 2016 and 2023, SPMS diagnoses in the Czech Republic shifted toward older patients with greater prior DMT exposure, particularly to HE-DMTs. The increase in clinical SPMS diagnoses from 2021 onward coincides with siponimod reimbursement and may reflect changing diagnostic behavior. Persistent discordance between clinical and algorithmic classifications underscores the need for more standardized SPMS identification criteria."

Late-breaking abstract • Reimbursement • US reimbursement • CNS Disorders • Multiple Sclerosis

Risk of Seizures in People with Secondary Progressive Multiple Sclerosis Treated with Siponimod and Fampridine (ECTRIMS 2025) - "One patient chose to change treatment from siponimod to off label ocrelizumab due to seizure risk. The findings suggest that combined use of siponimod and fampridine may increase the risk of seizures in MS patients. Clinicians should provide appropriate counselling to patients considering this combined therapy. In a patient group in whom licensed therapies are limited, this highlights the need for more available treatments to manage active progressive MS."

CNS Disorders • Epilepsy • Multiple Sclerosis

Effectiveness and safety of ofatumumab in treatment-naive and oral DMT-switched multiple sclerosis patients: a multicenter observational study in China (ECTRIMS 2025) - "Objectives/Aims: We conducted a multicenter observational study to evaluate the effectiveness and safety of ofatumumab in RMS patients who were either treatment-naïve or had switched from oral DMTs, including siponimod, fingolimod, teriflunomide and dimethyl fumarate... This real-world study revealed a significant decrease in disease activity and progression among MS patients treated with ofatumumab, including treatment-naïve and oral DMTs-switched patients, while maintaining a well-tolerated safety profile."

Clinical • Observational data • CNS Disorders • Multiple Sclerosis

Comparative Analysis of Ofatumumab versus Low-Medium Efficacy Disease Modifying Therapies in Multiple Sclerosis: Serum Neurofilament Light and Three-Year Clinical Outcomes (ECTRIMS 2025) - "The low-medium efficacy treatment group (group 2) included patients receiving BRACE therapies, teriflunomide, dimethyl fumarate, siponimod, fingolimod and cladribine... This real-world study demonstrates significantly higher NEDA-3 rates with ofatumumab compared to low-medium efficacy DMTs in RRMS patients. Although baseline sNfL levels were lower in the ofatumumab group, this difference did not reach statistical significance, and further research with a larger sample size is warranted. Additionally, a single baseline sNfL measurement was not a reliable predictor of clinical outcomes over the 2.6-year follow-up period, which may also be related to a small study population."

Clinical • Clinical data • CNS Disorders • Multiple Sclerosis

Treatment satisfaction of SPMS patients in Germany switching to siponimod from low efficacy therapies or fingolimod (ECTRIMS 2025) - "Previous medication influences treatment satisfaction as evaluated by the TSQM. Patients switching to siponimod from interferone, glatiramer acetate, or dimethyl fumarate exhibit lower levels of satisfaction compared to those switching from fingolimod. However, from baseline to 36 months of siponimod treatment, there is a notable increase in satisfaction in patients previously treated with IFN/GA and DMF."

Clinical • CNS Disorders • Multiple Sclerosis

Exit Strategies from Siponimod in SPMS Patients: Addressing Treatment Gaps in a Real-World Setting (ECTRIMS 2025) - "Among those who discontinued, 29 patients (61.7%) transitioned to alternative therapies—specifically, ocrelizumab was prescribed in 31.0% of cases, rituximab in 17.2%, and cladribine in 17.2%—while the remaining 18 patients (38.3%) did not initiate any subsequent DMTs. A significant treatment gap persists for patients discontinuing siponimod, underscoring the need for comprehensive risk-benefit strategies and structured transition protocols. Ocrelizumab emerges as the predominant alternative, highlighting its potential role in addressing this unmet therapeutic need."

Clinical • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Short washout from sequestering to depleting agents in multiple sclerosis is effective and safe: the FAST experience (ECTRIMS 2025) - "9 patients shifted from fingolimod and 1 from siponimod; 55% started IV anti-CD20. Rapid switch within 14 days from S1Pm to anti-CD20 therapies is an effective strategy to minimise the risk of rebound. Short WP does not negatively affect immune reconstitution, nor is it associated with increased frequency or severity of AEs. A larger sample size and longer follow-up are needed to confirm the absence of impact of short WP on safety and efficacy of B-cell depleting agents"

CNS Disorders • Infectious Disease • Multiple Sclerosis • Respiratory Diseases • CD4 • CD8

Safety profile of siponimod in patients with secondary progressive multiple sclerosis: A retrospective real-world analysis (ECTRIMS 2025) - "Siponimod treatment in patients with SPMS is associated with a high incidence of lymphopenia and various other side effects. Regular monitoring of lymphocyte count, OCT of the macula, dermatological evaluation, and individualized risk assessment are essential for the safe and effective use of siponimod."

Real-world • Real-world evidence • Retrospective data • Cardiovascular • CNS Disorders • Epilepsy • Hypertension • Infectious Disease • Macular Edema • Multiple Sclerosis • Ophthalmology • Otorhinolaryngology • Skin Cancer • Vertigo

The current use of Glial fibrillary acidic protein (GFAP) as an outcome in randomized clinical trials: a systematic review (ECTRIMS 2025) - "For data from one RCT a statistically significant decrease by 7.4 pg/mL with siponimod treatment (p<0.0001) versus placebo was reported... GFAP is increasingly used as an outcome in randomized MS clinical trials. Although data remain limited, RCTs reporting results have shown reductions in GFAP levels due to treatment. This consistent trend raises the question of whether GFAP reductions align with other outcome measures – a focus of ongoing analyses which will be presented at the conference to inform the potential clinical utility of GFAP."

Clinical • Review • Fatigue • Multiple Sclerosis • GFAP • NEFL