siponimod / Generic mfg. - LARVOL DELTA

Alterations in Sphingolipid Pathway Associate with Clinical Outcomes after Intracerebral Hemorrhage (ISC 2026) - "S1P receptor modulators (fingolimod, Siponimod) reduced edema and improved recovery in preclinical and early-phase trials. These novel exploratory findings suggest that dysregulation of sphingolipid metabolism may contribute to ICH outcomes. Reduced S1P in poor-outcome lobar ICH, appearing as relatively higher levels in deep ICH, suggests a role for S1P signaling in secondary injury and recovery and highlights the need for validation in larger cohorts."

Clinical • Clinical data • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Metabolic Disorders

Intracerebral hemorrhage induces monocyte TNF signaling that is suppressed by Siponimod (BAF312): a single-cell transcriptomics study in patients. (PubMed, medRxiv) - "Notably, increased monocyte TNF signaling correlated with better functional outcome, possibly related to the positive role of monocytes during the subacute stage of ICH. These findings suggest that BAF312 suppresses peripheral immune responses after ICH and supports a complex role of monocytes in this disease."

Journal • Cerebral Hemorrhage • Hematological Disorders • Inflammation

Effect of Sphingosine-1-Phosphate Receptor Modulators on Insulin Resistance: A Review. (PubMed, Ann Pharmacother) - "S1PR modulators are effective disease-modifying therapies in multiple sclerosis, but emerging evidence suggests a possible impact on insulin signaling and glucose metabolism. Vigilance in metabolic monitoring is recommended, particularly in patients with diabetes or other risk factors for insulin resistance."

Journal • Review • CNS Disorders • Diabetes • Metabolic Disorders • Multiple Sclerosis • Type 1 Diabetes Mellitus • IR

Novartis has signed an agreement with the US government aimed at lowering the prices of innovative medicines while continuing investment in domestic research and manufacturing. (Digital Health) - "Under the terms, Novartis will launch future medicines at prices comparable to other high-income countries and establish direct-to-patient platforms for Tabrecta (capmatinib), Mayzent (siponimod), and Rydapt (midostaurin), accessible via TrumpRx. The company will also pursue participation in the GENEROUS (GENErating cost Reductions fOr U.S. Medicaid) Model to improve medicine access for Medicaid patients."

Commercial • Acute Myelogenous Leukemia • Mast Cell Leukemia • Multiple Sclerosis • Non Small Cell Lung Cancer

ITASIA: Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy (clinicaltrials.gov) - P=N/A | N=134 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Jul 2025 | Trial primary completion date: Jun 2026 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Novartis and US government reach agreement on lowering drug prices in the US (Novartis Press Release) - "Novartis has voluntarily agreed to take actions aimed at meeting the US Administration’s drug pricing priorities, including: (i) Launching future medicines with comparable prices across high-income countries; (ii) Building direct-to-patient platforms for Mayzent (siponimod), Rydapt (midostaurin) and Tabrecta (capmatinib). These new platforms will be accessible through TrumpRx; (iii) Applying to participate in the GENEROUS (GENErating cost Reductions fOr U.S. Medicaid) Model aimed at further improving access to medicines in the US Medicaid program."

Commercial • Acute Myelogenous Leukemia • Aggressive Systemic Mastocytosis • Multiple Sclerosis • Non Small Cell Lung Cancer

Cellular and humoral vaccination response under immunotherapies-German consensus on vaccination strategies in neurological autoimmune diseases. (PubMed, Ther Adv Neurol Disord) - "The specific humoral and cellular response to vaccination can be compromised under alemtuzumab, azathioprine, cladribine, cyclophosphamide, CD19/CD20 antibodies (inebilizumab, ocrelizumab, ofatumumab, rituximab, ublituximab), dimethyl fumarate/diroximel fumarate, FcRn inhibitors (efgartigimod, rozanolixizumab), complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan), interleukin-6 receptor antibodies (tocilizumab, satralizumab), intravenous immunoglobulins, long-term steroid administration, methotrexate, mitoxantrone, mycophenolate mofetil, tacrolimus, teriflunomide, tumor necrosis factor-α blockers, and sphingosine-1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, siponimod), as well as after autologous stem cell transplantation...However, the humoral and cellular vaccination response may be impaired under immunotherapy necessitating close monitoring. Here, we provide applicable recommendations to optimize immunization for individuals receiving..."

Journal • CNS Disorders • Immunology • Infectious Disease • Oncology • Transplantation • IL6R

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