fingolimod / Generic mfg. - LARVOL DELTA

Asparagine Regulated by the Gut Microbiota Constrains Dendritic Cell Antigen Presentation and Response to anti-PD-1 Therapy in Microsatellite Stable Colorectal Cancer (IASGO 2026) - "CD8⁺ T cell depletion, MHC-I blockade, tumor draining lymph node (TDLN)resection, FTY720 treatment and asparagine supplementation were used to test functionalrequirements. Conclusions : Oral vancomycin sensitizes MSS CRC to anti-PD-1 therapy by remodeling the gutmicrobiota and lowering asparagine availability, which restores DC mediated cross-presentation andTDLN dependent CD8⁺ T cell priming. These findings define an asparagine–FBXO21–NF-κB2 axis as amicrobiota responsive mechanism of anti-PD-1 resistance and nominate oral vancomycin and DC FBXO21/p100 signaling as clinically tractable strategies or biomarkers for improving immunotherapyresponse in MSS CRC."

Gut Microbiota • IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD8 • IFNG • TNFA

Errate: Nasal Mucociliary Clearance and Its Relationship With Disease Severity in Patients With Multiple Sclerosis. (PubMed, Med Sci Monit) - "In the published version of Figure 2, the bars representing the Ocrelizumab and Fingolimod treatment groups were inadvertently interchanged. 2026; 32:e952850. DOI: 10.12659/MSM.952850."

Journal • CNS Disorders • Multiple Sclerosis

Predictors of high- versus low-intensity first-line multiple sclerosis treatments. (PubMed, Mult Scler J Exp Transl Clin) - "The first DMT filled was classified as either high- (natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine) or low-intensity (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, ozanimod)...The minority of MS patients initiated high-intensity treatment although this proportion increased over time, and later years were predictive of high-intensity treatment. Providers had a significant role in the approach selected."

Journal • CNS Disorders • Multiple Sclerosis

Fingolimod for Type 2 Diabetes Mellitus (clinicaltrials.gov) - P4 | N=40 | Recruiting | Sponsor: General Hospital of Shenyang Military Region | Trial completion date: Mar 2026 ➔ Mar 2028 | Trial primary completion date: Mar 2026 ➔ Mar 2028

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Anti-CTLA-4 antibody potentiates the antitumor effect of armed oncolytic virus OVM18 via enhancing intratumoral IL-18R1+CD8+ T cells. (PubMed, J Immunother Cancer) - "Our findings establish IL-18R1+CD8+ T cells as an important effector population in OVM18 therapy, thereby providing a strong rationale for combining OVM18 with CTLA-4 blockade to overcome therapeutic resistance and achieve durable antitumor responses."

IO biomarker • Journal • Oncology • BATF3 • CD8 • IL12A • IL18

Blocking the gut-liver IgA axis attenuates macrophage-mediated inflammation and injury in alcohol-associated liver disease. (PubMed, Gut) - "IgA binding to hepatic myeloid cells is associated with interleukin (IL)-1-linked inflammation in ALD, and in ethanol-fed mice pharmacologic modulation of immune-cell trafficking was accompanied by reduced IgA-bound hepatic myeloid cells and attenuated IL-1-related inflammation."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Failure • Oncology • CD14 • CD68 • IL1B

Association of HALP score with clinical and radiological activity following fingolimod discontinuation in patients with multiple sclerosis. (PubMed, eNeurologicalSci) - "•Fingolimod is an effective treatment option for Multiple Sclerosis(MS), but controlled or uncontrolled discontinuation can lead to serious clinical and radiological deterioration, processed as Rebound Activity(RA), especially in young female MS patients for pregnancy reason.•The HALP Score, as a nutritional and inflammatory biomarker, can be lower in individuals with MS compared to healthy control groups.•Conversely, a higher HALP score was found in the group with clinical and radiological activity after discontinuation of Fingolimod compared to the group without activity.•An increase in the HALP score in these situations may indicate properties reflecting an intense inflammatory process and may suggest a strong response following drug discontinuation.•It can reveal also that, in MS, the inflammatory period during which disease-modifying therapies are effective-namely, the "window of opportunity"-may be more dominant in patients exhibiting RA.•Similarly..."

Journal • CNS Disorders • Multiple Sclerosis

Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives. (PubMed, Front Immunol) - "In contrast, small-molecule DMTs such as fingolimod and teriflunomide provide greater dosing convenience and flexibility; however, their broad immunosuppressive effects often lead to treatment-induced lymphopenia and increased susceptibility to infections. Building on this evidence, this review examines the GSNO/GSNOR axis as an emerging therapeutic target in MS, highlighting its mechanistic roles in selective immune modulation, the regulation of neuroinflammation, and the attenuation of oxidative stress. Furthermore, we discuss the translational potential of reversible GSNOR inhibitors, which have demonstrated favorable safety and tolerability in Phase I/II studies for asthma and cystic fibrosis, while emphasizing the need for future clinical evaluation of their therapeutic efficacy in MS."

Journal • Review • Asthma • CNS Disorders • Cystic Fibrosis • Genetic Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases • HIF1A • IL6

Cardiac arrhythmias associated with S1PRMs: a pharmacovigilance study based on real-world data. (PubMed, Front Pharmacol) - "We identified 2,059 arrhythmia-related adverse events associated with S1PRMs, including 1,860 cases for fingolimod, 153 for siponimod, 38 for ozanimod, and 8 for ponesimod. As a disproportionality analysis of spontaneous reports, these results reflect statistical associations rather than causal relationships and should be regarded as hypothesis-generating; cross-drug comparisons are further influenced by differential reporting, market duration and cumulative exposure. These results may complement clinical trial data for informed risk-benefit assessment, particularly for newer S1PRMs with limited post-marketing surveillance data."

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

Aegle marmelos neuroprotective potential in demyelination rat model through modulation of BDNF, GDNF, HSP-90 and HSP-60. (PubMed, Inflammopharmacology) - "Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg)...Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg)...According to histopathological examination, AME-treated groups showed less demyelination and plaque formation with preserved neuronal architecture. By concurrently reducing oxidative stress, neuroinflammation, and promoting remyelination, these results show that AME exhibits strong neuroprotection."

Journal • Preclinical • CNS Disorders • Inflammation • Multiple Sclerosis • BDNF • HSP90AA1

The multifactorial nature of reproductive decision-making among women with multiple sclerosis. (PubMed, Eur J Midwifery) - "These findings suggest that reproductive decision-making among women with MS may involve multiple disease-related, psychological, and relationship-related considerations. Further studies with larger sample sizes are needed to confirm these associations."

Journal • CNS Disorders • Multiple Sclerosis

A stochastic agent-based model for naive CD8± T cell recirculation dynamics in mice. (PubMed, J Theor Biol) - "The robustness of the model was demonstrated by simulating the effect of FTY720 drug on T cell counts in the bloodstream at two different drug doses and over the span of one week, which is much longer than the original training period. This work offers a novel tool for quantifying T cell recirculation parameters and enables predictive capabilities for T cell dynamics."

Journal • Preclinical • CD8

Fungal Infections Associated with Sphingosine 1-Phosphate Receptor Modulators: Immunological Mechanisms, Clinical Patterns, and Management Considerations. (PubMed, Microorganisms) - "Fungal infections constitute a large portion of serious infections worldwide and are increasing, partially due to new immunomodulatory therapies, such as Sphingosine-1-Phosphate (S1P) receptor modulators, including fingolimod for the treatment of multiple sclerosis (MS)...Decisions regarding interruption or discontinuation of MS therapy should be individualized according to the clinical syndrome, infection severity, and risk of MS rebound. This narrative review synthesizes the available mechanistic and clinical evidence on invasive fungal infections in patients with multiple sclerosis receiving S1P receptor modulator therapy."

Journal • Review • CNS Disorders • Infectious Disease • Multiple Sclerosis • Respiratory Diseases • S1PR1 • S1PR5

DDI-4 induces a temperature-sensitive exocytotic remodeling during C. elegans spermiogenesis via nsun-2-dependent sphingosine signaling. (PubMed, PLoS Genet) - "Moreover, we tested sphingosine (SPH) and its analog FTY720 as MOF activators, using mutants lacking sphk-1 or spin-4, which encodes a transporter of phosphorylated SPH...Because DDI-4 lacks hydroxyl groups that SPHKs typically phosphorylate, these findings suggest that SPHK-1 may function not only as a kinase but also as a scaffold for downstream signaling. Together, our results reveal a temperature-sensitive, NSUN-2-dependent SPH-mediated signaling axis that regulates organelle exocytosis during spermiogenesis and suggest an evolutionarily conserved mechanism underlying fertilization competence."

Journal

Real-world siponimod use in secondary progressive multiple sclerosis: the RESYZE study. (PubMed, Ther Adv Neurol Disord) - "Prior to siponimod, 44.3% received highly effective therapies: fingolimod (20.5%), rituximab (9.5%), ocrelizumab (5.2%), natalizumab (4.8%), and alemtuzumab (2.4%). In the study cohort, pwSPMS had high disability scores and comorbidities; more than half were unable to work, and over 40% had previously received high-efficacy therapies. After 1 year of siponimod treatment, most pwSPMS showed no signs of disease activity, with stabilized EDSS scores and relapses and new T2 or gadolinium-T1 lesions, as well as a favorable safety profile."

Clinical • Journal • Real-world evidence • CNS Disorders • Dyslipidemia • Mental Retardation • Metabolic Disorders • Multiple Sclerosis • Psychiatry

Dose-dependent effects of fingolimod on behavioral, molecular, and Stereological outcomes in a rat model of intracerebroventricular streptozotocin-induced Alzheimer's disease-like cognitive dysfunction. (PubMed, 3 Biotech) - "These findings suggest beneficial effects within the doses examined, although additional dose-response studies are needed to determine the optimal therapeutic range. The online version contains supplementary material available at 10.1007/s13205-026-05015-3."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Oncology • BDNF • IL1B • IL6 • TNFA

Chemistry and biology of blocking sphingosine-1-phosphate (ACS-Fall 2026) - "In profiling our lead S1P transport blocker (STB), SLF80821178 (IC50 50 nM), we found that SLF80821178 is efficacious in a multiple sclerosis model but – unlike the SRM fingolimod – neither decreases heart rate nor compromises lung endothelial barrier function...In contrast to results obtained with Spns2 deficient mice, lymph S1P concentrations were not significantly changed in response to administration of STBs at doses that evoke maximal lymphopenia. Finally, cryo-EM characterization of SLF80821178 bound to Spns2 demonstrate binding in the S1P channel with key amino acid interactions with the compound."

CNS Disorders • Multiple Sclerosis

Novel Sphingosine Kinase 1 inhibitor promotes colorectal cancer cell death through apoptosis and autophagy | Poster Board #1235 (ACS-Fall 2026) - "In an effort to enhance the anticancer efficacy of the FTY720 scaffold, 29 novel analogs were synthesized by introducing amide or bioisosteric triazole motifs into an FTY720 intermediate...Furthermore, in vivo evaluation of two lead compounds revealed significant antitumor activity in colorectal cancer models. These results suggest that the incorporation of amide and triazole moieties effectively yields metabolically stable SK inhibitors, providing a promising chemical scaffold for the further development of colorectal cancer therapeutics."

Colorectal Cancer • Oncology • Solid Tumor • SPHK1

Single-Cell Profiling Identifies Skin-Resident Memory CD4+ T Cells as a Potential Correlate of Immunity During Staphylococcus aureus Skin Infection. (PubMed, Eur J Immunol) - "Upon reinfection, protective immunity was associated with rapid recall responses from these resident cells and was maintained despite FTY720-mediated blockade of lymphocyte egress from secondary lymphoid organs, demonstrating that circulating lymphocytes were dispensable for protection. Together, these findings identify infection-induced CD4+ Trms as a durable component of immune memory following S. aureus SSTI and support a role for tissue-resident immunity in protection against recurrent infection, highlighting CD4+ Trms as a potential target for future vaccine strategies."

Journal • Dermatology • Infectious Disease • CD4

Comparative multi-analyte serum protein differences between generic and brand-name dimethyl fumarate, fingolimod, and teriflunomide in multiple sclerosis. (PubMed, Clin Immunol) - "We compared biomarker variability in MS individuals (n = 1124) treated with generic or brand-name fumarates (diroximel fumarate, dimethyl fumarate (DMF)), fingolimod, and teriflunomide...Additionally, all generic DMTs demonstrated higher multi-variable variability index values across 18 proteins associated with MS disease activity. Greater biomarker variability with generic formulations may reflect differences in therapeutic exposure and less consistent disease control."

Journal • CNS Disorders • Multiple Sclerosis • CCL20 • CXCL13 • CXCL9 • TNFSF13B

Natalizumab and Tyruko (natalizumab biosimilar) for treating highly active relapsing-remitting multiple sclerosis after at least one disease-modifying therapy: a systematic review and economic model. (PubMed, Health Technol Assess) - "Fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b and peginterferon beta-1a were associated with an increased treatment discontinuation (29 studies, 13 interventions)...Data in highly active relapsing-remitting multiple sclerosis were available for fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, autologous haematopoietic stem cell treatment and placebo...60. See the NIHR Funding and Awards website for further award information."

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

SGPL1 Deficiency and the Limits of S1P Receptor Modulation: First Report of Fingolimod Administration (SSIEM 2026) - "This case demonstrates that S1P receptor modulation alone is insufficient to halt neurodegeneration in SPLIS. These findings underscore the urgent need for substrate reduction strategies or gene therapy — rather than downstream receptor modulation. Early diagnosis, guided by the recognition of adrenal calcification and multisystemic involvement, remains essential to enable timely intervention, particularly in patients harboring PLP-responsive mutations, before irreversible neurodegeneration is established."

Atopic Dermatitis • CNS Disorders • Dyslipidemia • Endocrine Disorders • Gene Therapies • Glomerulonephritis • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Neuralgia • Renal Disease • Respiratory Diseases • Vitiligo

Prophylactic Fingolimod Administration Prevents the Development of Proliferative Vitreoretinopathy in an Experimental Rat Model. (PubMed, Exp Eye Res) - "To the best of our knowledge, this proof-of-concept study provides the first preclinical evidence that prophylactic fingolimod administration effectively prevents PVR development, consistent with anti-inflammatory and immunomodulatory mechanisms. Thus, Fingolimod represents a promising prophylactic candidate for PVR prevention, warranting further clinical investigation."

Journal • Preclinical • Fibrosis • Immunology • Retinal Disorders

Severe hyponatremia masking cryptococcal meningitis in a fingolimod-treated patient: a case report. (PubMed, AME Case Rep) - "Dual antifungal therapy with liposomal amphotericin B and flucytosine was initiated. The patient's systemic symptoms and altered mentation subsequently resolved without sequelae. In patients receiving fingolimod who present with subacute altered mental status and severe hyponatremia, clinicians should maintain a high index of suspicion for cryptococcal meningitis and consider early cerebrospinal fluid evaluation, even in the absence of fever or meningeal signs."

Journal • Cardiovascular • CNS Disorders • Heart Failure • Human Immunodeficiency Virus • Infectious Disease • Multiple Sclerosis

A tumor microenvironment-responsive calcium overload nanoplatform inducing PANoptosis for enhanced cancer immunotherapy. (PubMed, Mater Today Bio) - "This orchestrated immune response markedly suppresses tumor growth and when combined with anti-PD-L1 therapy, induces a pronounced abscopal effect. Together, our results indicate that calcium overload, FTY720-mediated TRPM7 inhibition, and MnO2-induced redox imbalance can drive PANoptosis, offering a new concept for enhancing cancer immunotherapy."

Biomarker • Journal • Oncology • TRPM7