frexalimab (SAR441344) / ImmuNext, Sanofi, Royalty - LARVOL DELTA

Psychometric validation of PROMIS-Fatigue-MS-8a and MSIS-29v2 questionnaires in relapsing multiple sclerosis participants enrolled in a phase 2 trial of frexalimab. (PubMed, Mult Scler Relat Disord) - P2 | "PROMIS-Fatigue-MS-8a and MSIS-29v2 are valid and reliable measures for evaluating treatment benefits in clinical trials of RMS."

Journal • P2 data • CNS Disorders • Fatigue • Multiple Sclerosis

FREXADIGITAL AI Substudy: AI-based Smartphone Video Assessments of Motor Function in RMS and nrSPMS Population (AAN 2026) - P3 | "The FREXADIGITAL AI substudy pioneered vAI-based assessment and analysis for disease monitoring and treatment response in MS clinical trials.Design/ FREXADIGITAL AI is an optional exploratory substudy of the phase 3 FREXALT (RMS) and FREVIVA (nrSPMS) studies comparing the efficacy and safety of frexalimab to teriflunomide (FREXALT, NCT06141473) and/or placebo (FREVIVA, NCT06141486) over 24 months. This innovative approach offers a non-invasive, patient-centric, objective, standardized, and accessible method to estimate disease progression and treatment efficacy in people with MS."

Clinical • Video • CNS Disorders • Multiple Sclerosis

Long-term Treatment Effects of Frexalimab on NfL, CXCL13, and Brain Volume Loss in Relapsing Multiple Sclerosis (AAN 2026) - P2 | "Three years of frexalimab treatment demonstrated marked reductions in NfL and CXCL13, and limited BVL in pwRMS. These data contribute to understanding the effect of frexalimab on neuroinflammation and neurodegeneration, and support further investigations in both RMS and non-relapsing secondary progressive MS."

CNS Disorders • Inflammation • Multiple Sclerosis • CD40LG • CXCL13 • NEFL • Plasma NfL

Efficacy and Safety of Frexalimab in Participants With Relapsing Multiple Sclerosis: Three-year Results From the Phase Two Open-label Extension (AAN 2026) - P2 | "Frexalimab continues to exert sustained reduction in disease activity with favourable safety in pwRMS through 3 years, supporting its further development in phase 3 trials (FREXALT and FREVIVA) as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • CNS Disorders • Multiple Sclerosis • CD40LG

FREXERA: A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation (clinicaltrials.gov) - P2/3 | N=526 | Not yet recruiting | Sponsor: Sanofi

New P2/3 trial • Immunology • Transplant Rejection • Transplantation

Frexalimab in Relapsing Multiple Sclerosis and Non-Relapsing Secondary Progressive Multiple Sclerosis: Design of the Phase 3 FREXCITE Trial (ACTRIMS Forum 2026) - P2, P3 | "This FREXCITE Phase 3 bridging study will assess the PK non-inferiority, safety, efficacy, and patient experience of frexalimab administered SC using OBDS compared to IV administration in participants with RMS and nrSPMS, supporting a more convenient route of administration for those requiring long-term frexalimab therapy."

P3 data • CNS Disorders • Inflammation • Multiple Sclerosis • CD40LG

Long-term Frexalimab Treatment Modulates the Activity of Immune Networks (ACTRIMS Forum 2026) - P2 | "Long-term frexalimab treatment exerts comprehensive immunomodulatory effects by downregulating inflammatory mediators associated with disease progression. These findings support the emerging understanding of frexalimab’s mechanism of action, which targets immune networks involving adaptive and innate immunity, and holds a potential to mitigate both acute and smoldering neuroinflammation in MS."

IO biomarker • CNS Disorders • Inflammation • Multiple Sclerosis • CD27 • CD40LG • CSF1R • CXCL13 • GZMA

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • CNS Disorders • Multiple Sclerosis

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: Sanofi

Head-to-Head • New P3 trial • CNS Disorders • Multiple Sclerosis

FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS) (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: Sanofi | Trial completion date: Aug 2031 ➔ Oct 2030

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS) (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: Sanofi | Trial completion date: Oct 2028 ➔ Aug 2031

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions. (PubMed, Int J Mol Sci) - "Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • Movement Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Parkinson's Disease • Rare Diseases • CD20 • CD52 • IL6

ECTRIMS 2025: Frexalimab shows long-term benefits for MS patients (Multiple Sclerosis News Today) - "The data showed that rates of new or enlarging lesions and of lesions with active inflammation remained low through 120 weeks, or about 2.5 years...Relapse rates were also low — with 88% of participants on a high dose of frexalimab remaining relapse-free — and disability scores remained stable throughout the studies, the data showed...In this part, both frexalimab groups had significantly fewer lesions with active inflammation (up to 89% less), as well as new and enlarging lesions (up to 92% less) than the placebo....Relapse rates were also low across groups, though the lowest relapse rate — 0.09 relapses per year — was observed in the patient group who were always on the high, intravenous dose of frexalimab."

P2 data • Multiple Sclerosis

SCD40L in Cerebrospinal Fluid Before and After Autologous Hematopoietic Stem Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (ECTRIMS 2025) - "A recent phase II trial showed that the CD40L monoclonal antibody frexalimab significantly reduced active lesions in relapsing-remitting MS (RRMS)...Patients had received a median of two prior DMTs; 14% were treatment-naïve, 36% had received 1st line, and 50% 2nd line treatment (natalizumab or rituximab)... sCD40L is elevated in MS, correlates with disease activity, and decreases after AHSCT. Baseline sCD40L may be a prognostic biomarker for post-transplant inflammatory activity."

IO biomarker • Bone Marrow Transplantation • CNS Disorders • Inflammation • Multiple Sclerosis • Transplantation • CD40LG

Meningeal B cell aggregates are targeted by an antibody to CD40L in a spontaneous animal model of MS (ECTRIMS 2025) - "Recently, anti-CD40L antibody frexalimab, was shown to reduce disease activity in MS patients... In conclusion, anti-CD40L treatment might be beneficial in progressive MS as it can potentially eliminate meningeal B cell aggregates, prevent astrocyte damage and increase anti-inflammatory properties of immune cells within the CNS compartment."

Preclinical • Multiple Sclerosis • Solid Tumor • CD40LG • IL10

Safety and Efficacy of Frexalimab in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results From the Phase 2 Open-label Extension (ECTRIMS 2025) - P2 | "Frexalimab continues to show favourable safety and sustained reduction in disease activity in pwRMS through 2.5 years, supporting its further development in phase 3 trials as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • P2 data • Back Pain • CNS Disorders • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Novel Coronavirus Disease • CD40LG

Frexalimab (CD40 ligand), glofitamab (CD20CD3), and others (ECTRIMS 2025) - No abstract available

CD40LG

Long-term Treatment Effect of Frexalimab on NfL and Plasma Biomarkers of Adaptive and Innate Immunity (ECTRIMS 2025) - P2 | "These biomarker results support the emerging understanding of frexalimab's mechanism of action targeting the co-stimulation of adaptive and innate immune cells, thought to contribute to both acute and chronic neuroinflammation in MS."

Biomarker • IO biomarker • Inflammation • Multiple Sclerosis • CD27 • CD40LG • CXCL13 • NEFL • Plasma NfL

Safety and efficacy of frexalimab in relapsing multiple sclerosis: 2-Year results from phase 2 open-label extension (EAN 2025) - P2 | "Frexalimab continues to show favorable safety and sustained reduction in disease activity in pwRMS through W96, supporting its further development in phase-3 trials as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • CD40LG

Frexalimab reduces plasma neurofilament light chain in relapsing multiple sclerosis: Week 72 data from phase 2 trial (EAN 2025) - P2 | "The observed reduction in NfL through W72 indicates that frexalimab markedly reduces neuroaxonal damage in pwRMS."

IO biomarker • P2 data • CNS Disorders • Multiple Sclerosis • CD40LG • NEFL • Plasma NfL

The role of microglia in multiple sclerosis: implications for treatment with Bruton's tyrosine kinase inhibitors. (PubMed, Front Immunol) - "BTK inhibitors and other novel treatments for MS, including masitinib and frexalimab, show promise in modulating microglial function and influencing the disease progression rate. The multifaceted roles of microglia in CNS development, immune surveillance, and particularly in the pathogenesis of MS highlight the potential of targeting microglial functions in MS treatment. Emerging research on the involvement of microglia in MS pathophysiology offers promising avenues for developing novel therapies, especially for progressive MS, potentially improving patient outcomes in this debilitating disease."

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

Fabulinus-A randomized, controlled study with frexalimab to examine the endogenous insulin secretion with newly occurring type 1 diabetes stage 3 in adults and adolescents (DDG 2025) - P2 | "Fabulinus is an innovative combined proof-of-concept and dose finding study that is tailored to the specific requirements for clinical development to maintain ß cells at T1D. Encore submission. This study and support from Medical Writing financed by Sanofi."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD40LG

APATURA: Efficacy and Safety of Frexalimab (SAR441344) in the Treatment of Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=116 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Sep 2025 ➔ Jul 2026

Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety and Efficacy of Frexalimab from the Phase 2 Open-label Extension in Participants with Relapsing Multiple Sclerosis: 2-year Results (S3.006). (PubMed, Neurology) - P2 | "Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Bristows . Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Clinical • Journal • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Pain • CD40LG

Safety and Efficacy of Frexalimab from the Phase 2 Open-label Extension in Participants with Relapsing Multiple Sclerosis: 2-year Results (AAN 2025) - P2 | "Frexalimab continues to show favorable safety and sustained reduction in disease activity in pwRMS through W96, supporting its further development in phase 3 trials as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Pain • CD40LG