Ponvory (ponesimod) / Idorsia, J&J, Juvise Pharma, Vanda - LARVOL DELTA

Comparative Effectiveness of Fumarates Versus Sphingosine-1-Phosphate Receptor Modulators in Black Patients with Multiple Sclerosis. (PubMed, Neurol Ther) - "This real-world, claims-based analysis demonstrates that fumarates and S1P receptor modulators have similar effectiveness in reducing relapses among Black PwMS, with > 72% of patients in both treatment groups remaining relapse-free at 24 months. Given the underrepresentation of Black patients in MS clinical trials, these results provide valuable real-world evidence to guide treatment decisions for this population."

HEOR • Journal • CNS Disorders • Multiple Sclerosis

OTIMUM Phase 3 Extension Further Highlights Sustained Efficacy, Safety of Ponesimod (NeurologyLive) - P3 | N=877 | OPTIMUM-LT (NCT03232073) | Sponsor: Actelion | "Newly reported data from the phase 3 OPTIMUM-LT open-label extension trial (NCT03232073) showed that treatment with ponesimod (Ponvory; Vanda Pharmaceuticals) was safe and led to sustained reduction in relapses, MRI lesions, and low disability accumulation among patients with relapsing multiple sclerosis over a long-term period....Within this group, results showed an annualized relapse rate of 0.143 (95% CI, 0.123-0.167), with 56.7% of patients relapse-free over the combined analysis period, which lasted up to 8.2 years. Overall, the median time to relapse for the approved sphingosine-1-phosphate receptor (S1P) modulator was 402.71 weeks."

P3 data • Multiple Sclerosis

Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection (ASRI 2025) - "Furthermore, mice treated with Ponesimod, an inhibitor of T cell egress from lymph nodes, displayed reduced incidence of preterm birth... We propose a model whereby excessive maternal bladder inflammation in response to UTI drives immune cell trafficking to the lymph node and subsequent T cell activation at the maternofetal interface, triggering preterm labor. Further, we reveal the potential prognostic value of urine cytokine levels, with known or unknown culture status, for birth outcomes in a human cohort. Our unique bimodal murine model coupled with patient samples provides a platform to investigate immunological and microbial factors governing UTI-associated preterm birth, revealing novel therapeutic opportunities to predict or prevent preterm birth."

Prematurity • Infectious Disease • Inflammation • Nephrology • Septic Shock • IL10 • IL15 • IL1B • IL1R1

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

Vanda Pharmaceuticals Reports First Quarter 2025 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $50.0 million in the first quarter of 2025, a 5% increase compared to $47.5 million in the first quarter of 2024. Fanapt net product sales were $23.5 million in the first quarter of 2025, a 14% increase compared to $20.6 million in the first quarter of 2024. HETLIOZ net product sales were $20.9 million in the first quarter of 2025, a 4% increase compared to $20.1 million in the first quarter of 2024. PONVORY net product sales were $5.6 million in the first quarter of 2025, a decrease of 18% compared to $6.8 million in the first quarter of 2024."

Sales • Bipolar Disorder • Multiple Sclerosis • Sleep Disorder • Sleep Wake Cycle Disorder

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

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

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

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $53.2 million in the fourth quarter of 2024, a 17% increase compared to $45.3 million in the fourth quarter of 2023 and a 12% increase compared to $47.7 million in the third quarter of 2024."

Sales • CNS Disorders

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "PONVORY (ponesimod): Investigational New Drug (IND) applications for PONVORY in the treatments of psoriasis and ulcerative colitis were accepted by the FDA in the fourth quarter of 2024....Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025.....Imsidolimab: Vanda expects to initiate and complete the technology transfer activities in 2025 and immediately begin preparing the Biologics License Application (BLA) and MAA for generalized pustular psoriasis (GPP) for the US and EU. The imsidolimab BLA for GPP is expected to be submitted to the FDA in 2025."

EMA filing • FDA filing • IND • Immunology • Psoriasis • Ulcerative Colitis

PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates. (PubMed, Mol Imaging Biol) - "[18F]TZ4877 exhibits reversible kinetic properties, but the low fP value limits reproducible quantification with this radiotracer. S1PR1 is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies."

Journal • Anesthesia • S1PR1

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

Vanda Pharmaceuticals Reports Third Quarter 2024 Financial Results (PRNewswire) - "Vanda expects Investigational New Drug (IND) applications for PONVORY in the treatments of psoriasis and ulcerative colitis to be completed in the fourth quarter of 2024."

IND • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

Vanda Pharmaceuticals Reports Third Quarter 2024 Financial Results (PRNewswire) - "Third Quarter of 2024...PONVORY net product sales were $5.9 million in the third quarter of 2024, a decrease of 32% compared to $8.6 million in the second quarter of 2024. The acquisition of PONVORY from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company, was completed on December 7, 2023...First Nine Months of 2024...PONVORY net product sales were $21.3 million in the first nine months of 2024. The acquisition of PONVORY from Janssen was completed on December 7, 2023."

Sales • CNS Disorders • Immunology • Multiple Sclerosis

Targeting the pathogenic synergy of ceramide and S1P in Alzheimer’s disease (Neuroscience 2024) - "Using the 5XFAD familial AD mouse model, we inhibited Aβ-induced CREV secretion by astrocytes with the neutral sphingomyelinase 2 inhibitor GW4869 and restored Aβ clearance by microglia with the S1PR1 antagonist Ponesimod. These interventions significantly improved AD pathology and memory function in 5XFAD mice. Currently, we are testing additional drugs to target the synergy of ceramide and S1P, aiming to develop new approaches for AD therapy."

Alzheimer's Disease • CNS Disorders • S1PR1 • TLR4

Brain volume loss in relapsing multiple sclerosis: indirect treatment comparisons of available disease-modifying therapies. (PubMed, BMC Neurol) - "Limitations of these analyses included the potential for confounding due to pseudoatrophy, and a lack of long-term clinical data for BVL. Our findings suggest that important differences in BVL may exist between DMTs. Continued investigation of BVL in studies of RMS is important to complement traditional disability endpoints, and to foster a better understanding of the mechanisms by which DMTs can slow BVL."

Journal • CNS Disorders • Multiple Sclerosis

Incidence Rates of Immune Thrombocytopenic Purpura (ITP) and Autoimmune Hepatitis (AIH) in Multiple Sclerosis Patients Initiating Highly Efficacious Disease Modifying Therapy: A Cohort Study in US Claims Data (ECTRIMS 2024) - "Adult MS patients initiating any HE-DMT (including rituximab, alemtuzumab, ocrelizumab, cladribine, mitoxantrone, fingolimod, natalizumab, ofatumumab, ponesimod, ozanimod, and siponimod) between November 14, 2014, and June 30, 2023 were included... Incidence of ITP or AIH in MS patients initiated with HE-DMTs was rare. Active safety monitoring of new HE-DMT based on claims data necessitates a large dataset to detect rare adverse events and long-term follow-up."

Clinical • Autoimmune Hepatitis • CNS Disorders • Hematological Disorders • Hepatology • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Multiple Sclerosis • Thrombocytopenic Purpura

"Delayed high-efficacy therapy for multiple sclerosis increases risk of Sustained Decrease of Income" (ECTRIMS 2024) - "Now we are exploring the impact of high-efficacy therapy (HET) timing on the risk of developing SDI Objectives/Aims: We investigated the effect of delayed compared to early exposure to HET on MS patients' declared earnings as identified by SDI Our study includes incident relapsing-onset patients from the Swedish MS Registry, with onset between 2000 and 2018 with at least 3 years of recorded annual income after onset, who were exposed to HET (i.e., Alemtuzumab, Fingolimod, Mitoxantrone, Natalizumab, Ocrelizumab, Ozanimod, Ponesimod, Rituximab, Siponimod). Delayed exposure to high-efficacy therapy is linked to adverse outcomes in patients' work capabilities, as indicated by a significantly elevated risk of developing a sustained decrease of income. This novel income-based outcome measure serves as a valuable indicator of disease progression."

Clinical • CNS Disorders • Multiple Sclerosis

Determinants of time delay between recommendation for and start of high-efficacy treatment in Multiple Sclerosis (ECTRIMS 2024) - " Data of 160 patients who received a recommendation for HET (i.e. fingolimod, ponesimod, ozanimod, siponimod, cladribine, ofatumumab, ocrelizumab, natalizumab, rituximab) between 2015 and August 2023 at the University Hospital Frankfurt were extracted from electronic health reports and retrospectively analyzed... Our results suggest that older patients with a progressive phenotype, higher EDSS, higher number of prior DMTs and newly diagnosed chronic diseases after treatment recommendation experience significant time delay in treatment initiation. Further analysis will focus on investigating the dynamics of these factors and time delay periods across the different years, reflecting the accumulation of specific knowledge about the advantages of early HET initiation."

Clinical • CNS Disorders • Inflammation • Multiple Sclerosis

Mitochondrial effects of S1P receptor agonists: when blocking lymphocyte egress is not the whole picture (ECTRIMS 2024) - "Introduction: Fingolimod (FTY720), an analog of sphingo-sine-1-phosphate (S1P) that inhibits the egress of lymphocytes through the internalization of S1P receptors, is a non-selective S1PR agonist that induces sustained lymphopenia and accumulates in the CNS...Objectives/Aims: We aimed to compare the putatively inactive form with the phosphorylated compound and with other analogs (Siponimod and Ponesimod), as they bind to distinct S1P receptors and their effects may not be specific of a single subtype... The identification of the altered mitochondrial mechanisms underpinning these therapeutic drugs might be of remarkable relevance to MS."

Metabolic Disorders • MFN2 • PFKFB3

Comparing Lymphocyte Count among different S1P modulators in people With Multiple Sclerosis: a Multicenter Real-World Study (ECTRIMS 2024) - "Objectives/Aims: Our study aimed to assess the different degrees of lymphopenia consequent to the use of various S1P modulators: Ozanimod, Siponimod, Ponesimod, and Fingolimod. Our study is particularly important as it is the first real world head-to-head trial investigating this subject. We have succeeded in demonstrating a different degree of lymphopenia among S1P modulators. This detail is of extreme importance for the physician when choosing the drug to administer taking into consideration all the patient's characteristics."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Inflammation • Multiple Sclerosis

Hospital admissions due to infections in the national population of people with multiple sclerosis on disease-modifying therapies: Real-world data from NHS England (ECTRIMS 2024) - " There were 25,524 pwMS on a DMT: beta interferons (n=1589), cladribine (2238), dimethyl fumarate (3102), fingolimod (1311), glatiramer acetate (1648), natalizumab (3945), ocrelizumab (7751), ofatumumab (2498), ponesimod (66), siponimod (574), and teriflunomide (802)... These findings show the increased risk of serious infections associated with immunosuppressive DMTs in pwMS and highlight the need for further research to improve the safety profile of these treatments and develop guidelines on the prevention of infections in this population."

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