Mayzent (siponimod) / Novartis - LARVOL DELTA

Safety and tolerability of conversion to siponimod from other disease-modifying therapies in patients with advancing forms of relapsing MS: Results from the EXCHANGE study. (PubMed, Mult Scler) - P3 | "Conversion to siponimod from other DMTs was found to be generally well tolerated. Patients switching from other S1P-receptor modulators may be able to immediately transition to the siponimod maintenance dose without effects on HR."

Journal • Cardiovascular • CNS Disorders • Multiple Sclerosis • Pain

Lymphopenia associated with sphingosine 1-phosphate receptor modulators (S1PRMs) in multiple sclerosis: analysis of European pharmacovigilance data. (PubMed, Pharmacol Rep) - "The most relevant clinical implication of the disproportionality analysis is to increase the awareness of the risk of lymphopenia related to these drugs, thus supporting proactive monitoring and optimizing treatment strategies for people with MS."

Adverse events • Journal • CNS Disorders • Multiple Sclerosis

Effect of Sphingosine 1 Phosphate Receptor Modulators on Fatigue Among Multiple Sclerosis Patients (P6-1.017). (PubMed, Neurology) - "We found 5 studies, 3 of which were randomized to injectable DMT, Standard DMT (interferon and glatiramer acetate), and teriflunomide, respectively...Fingolimod and ponesimod were found to be effective in improving fatigue among PwMS; no studies have been found on ozanimod and Siponimod...The institution of Dr. Bernitsas has received research support from Roche/Genentech."

Clinical • Journal • Review • CNS Disorders • Fatigue • Multiple Sclerosis

Identifying cardiovascular toxicity associated with sphingosine 1-phosphate receptor modulators: A case-control study based on the FDA adverse event reporting system. (PubMed, Int Immunopharmacol) - "In this study, signals of bradyarrhythmias, hypertension, QT interval prolongation, central nervous system ischemia, tachyarrhythmias, and ischaemic heart disease were significant with one or more S1PR modulators, which warrant clinical attention and ongoing monitoring."

Adverse events • Journal • Cardiovascular • CNS Disorders • Coronary Artery Disease • Heart Failure • Hypertension • Multiple Sclerosis • Rare Diseases

Assessment of Real-World Adverse Events Associated with Ozanimod in Relapsing Remitting Multiple Sclerosis (RRMS) (ISPOR 2025) - "AE reports and patient outcomes were extracted for all instances where DMTs (ozanimod, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, teriflunomide, cladribine, alemtuzumab, natalizumab, ocrelizumab, ublituximab, and ofatumumab) were the 'primary suspect' for the AE... Based on this descriptive analysis of the FAERS data, ozanimod has a lower proportion of AEs linked to serious outcomes than the other DMTs. Ozanimod generally had a larger share of the ten labeled AEs compared with the other DMTs; however, these labeled AEs made up a small percentage of all the AEs reported for ozanimod and the other DMTs."

Adverse events • Clinical • Real-world • Real-world evidence • Back Pain • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Pain • Respiratory Diseases

Fatigue, depression, and QOL changes due to continuous administration of Siponimod (JSNE 2025) - No abstract available

CNS Disorders • Depression • Fatigue • Mood Disorders • Psychiatry

Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study. (PubMed, Neurol Clin Pract) - "We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs...Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections."

Adverse events • Journal • Real-world evidence • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Varicella Zoster

Effect of Sphingosine 1 Phosphate Receptor Modulators on Fatigue Among Multiple Sclerosis Patients (AAN 2025) - "We found 5 studies, 3 of which were randomized to injectable DMT, Standard DMT (interferon and glatiramer acetate), and teriflunomide, respectively. Fingolimod and ponesimod were found to be effective in improving fatigue among PwMS; no studies have been found on ozanimod and Siponimod. As fatigue has a complex and subjective nature, more studies are required."

Clinical • CNS Disorders • Fatigue • Multiple Sclerosis

Real World Cardiovascular Adverse Events of S1PR Modulators in Multiple Sclerosis (ACTRIMS Forum 2025) - "Background: There are four FDA approved S1PR modulators for treatment of multiple sclerosis (MS): Fingolimod, Siponimod, Ozanimod and Ponesimod. Bradycardia and conduction disorders were the most common cardiac adverse events across all S1PR modulators. Siponimod and Ozanimod were associated with significantly fewer cardiac AEs compared to Fingolimod. This study shows importance of considering the comorbidities and cardiac monitoring when prescribing S1PR modulators."

Adverse events • Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Disorders • Multiple Sclerosis

Ozanimod Does Not Directly Impact B Cell Activation, Proliferation, and Memory Recall in Human ex vivo Functional Assays (ACTRIMS Forum 2025) - "A recent retrospective analysis of the DAYBREAK study has demonstrated that all MS patients on ozanimod treatment effectively generate a vaccine-induced antibody response against SARS-CoV-2, though heterogeneity in the magnitude of serologic response was observed, with some patients developing lower antibody levels.Objectives: Our objective was to evaluate whether ozanimod, or other S1P receptor modulators (fingolimod, etrasimod, ponesimod and, siponimod), had a direct impact on primary human B cell function when assessing activation, proliferation, differentiation, and antibody memory recall. We utilized human peripheral blood mononuclear cells (PBMC) or isolated B cells from healthy donors. Results from this work suggest that ozanimod does not directly impact primary human B cell activation, proliferation, differentiation, or memory recall. Findings reinforce the observation that MS patients treated with ozanimod mount an effective immune response with 100%..."

Preclinical • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Respiratory Diseases • Tetanus • CCL3 • CD40LG • CD69 • CSF2 • CXCL8 • IL2 • IL21 • IL2RA • IL6 • TNFA

Baseline Characteristics Across Major Clinical Trials in Progressive Multiple Sclerosis: Insights from ORATORIO, EXPAND, MS-STAT2, HERCULES, and CALLIPER (ACTRIMS Forum 2025) - "Several major trials have explored therapies in this domain, including ORATORIO (ocrelizumab, primary progressive MS, PPMS), EXPAND (siponimod, secondary progressive MS, SPMS), MS-STAT2 (simvastatin, SPMS), and HERCULES (tolebrutinib, non-relapsing SPMS, nrSPMS). The data from this cohort could provide valuable insight into understanding the effects of vidofludimus calcium in a non-active and progressive population. Any impact of vidofludimus calcium on 24-week confirmed disability worsening in this group may therefore primarily reflect its influence on compartmentalized pathology within the CNS. Top line data of the study is expected in April 2025."

Clinical • CNS Disorders • Inflammation • Multiple Sclerosis • NR4A2 • STAT2

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Active, not recruiting | Sponsor: Johns Hopkins University | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

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

Siponimod inhibits microglial inflammasome activation. (PubMed, Neurosci Res) - "Our data indicate that siponimod achieves its anti-inflammatory effects by inhibiting inflammasome activation in microglia via S1P1 antagonism. This process is inferred to play a crucial role in mitigating the secondary progression of multiple sclerosis, where microglial activation in the gray matter is considered a key pathological factor."

Journal • CNS Disorders • Multiple Sclerosis • CASP1 • IL1B

MRI versus relapse: optimal activity monitoring for management of progressive multiple sclerosis. (PubMed, Brain Commun) - "We separately analysed retrospective data from patients with clinically diagnosed secondary progressive multiple sclerosis in the Adelphi Real-World Disease Specific Programme (a cross-sectional survey) in multiple sclerosis (Adelphi: n = 2554) and the placebo group of the Phase III EXploring the efficacy and safety of siponimod in PAtients with secoNDary progressive multiple sclerosis (EXPAND) trial, [EXPAND-PBO (placebo group of the EXPAND): n = 546] to assess: differences between active/non-active disease in the real-world (characteristics; monitoring); the value of MRI and relapse to indicate disease activity; and the number and characteristics of non-active patients with disease activity in the clinical study...However, in the real-world, fewer non-active patients had received an MRI in the last year than active patients, which is concerning given that most disease activity in EXPAND-PBO was identified via MRI. We highlight difficulties in consistently identifying..."

Journal • CNS Disorders • Inflammation • Multiple Sclerosis

Siponimod supports remyelination in the non-supportive environment. (PubMed, Sci Rep) - "This enhanced recovery was paralleled by the trend of lower densities of Ki67+ proliferating oligodendrocyte progenitor cells. Our findings suggest that Siponimod has modest pro-regenerative capacities, partly explaining the amelioration of disease progression in secondary progressive MS patients."

Journal • CNS Disorders • Multiple Sclerosis • Solid Tumor • MBP • OLIG2

Drug-related macular edema: a real-world FDA Adverse Event Reporting System database study. (PubMed, BMC Pharmacol Toxicol) - "This study utilizes the FAERS database to investigate potential associations between drug use and the occurrence of ME, rapidly identify drugs that may induce the condition, and propose research strategies. These findings hold significant value for guiding clinical medication practices."

Adverse events • Journal • Real-world evidence • Macular Edema • Ophthalmology

Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy. (PubMed, Mult Scler Relat Disord) - "This exploratory substudy supports further investigation of OCT measurement of retinal atrophy as a non-invasive potential biomarker of treatment effects on neurodegeneration in SPMS."

Journal • CNS Disorders • Multiple Sclerosis

Efficacy and safety of disease-modifying therapies in pediatric-onset multiple sclerosis: A systematic review of clinical trials and observational studies. (PubMed, Mult Scler Relat Disord) - "The number of DMTs approved for the treatment of POMS is limited, and some of the available DMTs are used off-label. The available evidence from published studies of varying reliability supports the efficacy of DMTs in POMS. However, well-designed, long-term RCTs in the pediatric population are needed. The results of ongoing studies may fill the existing gap in clinical evidence, possibly leading to the approval of more highly effective DMTs for patients with POMS."

Journal • Observational data • Review • CNS Disorders • Multiple Sclerosis • Pediatrics

Exploring Public Interest in Multiple Sclerosis and Its Treatment Measures in the United States: A Google Trends Analysis. (PubMed, Cureus) - "A notable increase in RSV was found for treatments such as rituximab, ocrelizumab, ublituximab, siponimod, and ponesimod in the 2019-2023 period compared to 2014-2018 (p  0.05)...The increased interest in recent treatments aligns with advancements in MS management and may influence patient inquiries and treatment decisions. These findings highlight the utility of Google Trends as a tool for monitoring public awareness and underscore the importance of providing accessible, accurate information to guide healthcare strategies and policymaking."

Journal • CNS Disorders • Multiple Sclerosis • Respiratory Syncytial Virus Infections

NEOS: Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=120 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Head-to-Head • CNS Disorders • Multiple Sclerosis • Pediatrics

The real-world safety assessment of Siponimod: A systematic analysis based on the FAERS database. (PubMed, J Neurol Sci) - No abstract available

Journal • Real-world evidence

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 • Hematological Disorders • Multiple Sclerosis

Survey Among Healthcare Professionals and MS Patients to Assess Their Understanding of RMP Materials (clinicaltrials.gov) - P=N/A | N=335 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2024 ➔ Feb 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

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

Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment. (PubMed, Ther Adv Neurol Disord) - "The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies."

Immunomodulating • Journal • CNS Disorders • Multiple Sclerosis • CD52

Unique pharmacological properties of etrasimod among S1P receptor modulators. (PubMed, FEBS Open Bio) - "Since differences in S1PR binding and downstream intracellular signaling could contribute to distinct profiles of drug efficacy and safety, we directly compared the S1P1-5 selectivity profile of etrasimod to three marketed S1PR modulators: fingolimod, ozanimod, and siponimod. Relatively lower potency of etrasimod in inducing G protein signaling corresponded to significantly diminished activation of human cardiac G protein-coupled inwardly rectifying potassium channels when compared to ozanimod. Together with pharmacokinetic properties, this hell profile of etrasimod may contribute to the positive benefit risk profile of etrasimod observed during the phase III ELEVATE UC 52 and ELEVATE UC 12 trials in patients with moderately to severely active ulcerative colitis."

Journal • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis