Briumvi (ublituximab-xiiy) / LFB SA, Ildong, TG Therap, Neuraxpharm - LARVOL DELTA

Modeling lymphocyte subset dynamics after ublituximab therapy in patients with multiple sclerosis: an Italian prospective study. (PubMed, Front Immunol) - "In our cohort, ublituximab induced rapid, durable CD19+ naive B-cell depletion with only transient, reversible effects on other lymphocyte subsets and preserved immunoglobulin levels. This signature extends to older and high BMI patients, supporting ublituximab as a versatile therapeutic option across heterogeneous MS populations."

Journal • CNS Disorders • Multiple Sclerosis • CD4 • CD8 • NCAM1

Comparative Efficacy of Ublitixumab Versus Natalizumab in the Treatment of Relapsing and Remitting Multiple Sclerosis. (PubMed, Cureus) - "Among these, monoclonal antibodies such as ublituximab and natalizumab have emerged as key therapeutic options with distinct mechanisms of action and safety profiles. This narrative review aims to compare the efficacy, safety, and clinical impact of ublituximab and natalizumab in the treatment of RRMS, providing insights into their role in individualized treatment strategies."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis

ENHANCE: Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: TG Therapeutics, Inc. | N=600 ➔ 800 | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Mar 2026 ➔ Sep 2026

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

Acalabrutinib, Umbralisib and Ublituximab Regimen (AU2) Demonstrates High Response Rate and Undetectable Molecular Minimal Residual Disease (MRD) in Patients (pts) with De Novo Mantle Cell Lymphoma (MCL) (ASH 2024) - P2 | "Two pts were switched to zanubrutinib due to PD on U2, both achieved response. AU2 is a highly effective regimen in pts with previously untreated MCL, including those with high-risk genetics (100% CR rate), and achieves a high molecular uMRD rate. Pts who develop progressive disease can be effectively salvaged with subsequent therapies."

Clinical • IO biomarker • Minimal residual disease • Residual disease • Alzheimer's Disease • CNS Disorders • Dementia • Genito-urinary Cancer • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Oncology • Prostate Cancer • Solid Tumor • TP53

A Phase 2 Study of Acalabrutinib, Umbralisib, and Ublituximab (AU2) in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (ASH 2023) - P2 | "Immune-related adverse events were frequently observed and required dose reduction of umbralisib in 38% of the patients but most were then able to stay on therapy. Longer follow-up is required to determine durability of remission off therapy."

IO biomarker • P2 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Richter's Syndrome • ATM • IGH • NOTCH1 • PIK3CD • SF3B1 • TP53

Clonal Evolution during Dual B Cell Receptor Pathway Inhibitor Therapy with Acalabrutinib and Umbralisib in CLL Patients (ASH 2024) - "We have reported interim results of a phase 2 study combining acalabrutinib with the PI3K inhibitor umbralisib for 6 months, followed by the addition of the anti-CD20 antibody ublituximab (AU2) for months 7-12, with end of therapy at 12 months for those in complete response (CR) or 24 months for others (Ahn et al., ASH 2023). Overall, these findings highlight that even in the setting of clinical response with dual BCR pathway inhibitor therapy, clonal evolution is ongoing in genes potentially associated with resistance. Further clinical follow-up of this study will be required to associate evolving mutations with duration of response or progression-free survival."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BIRC3 • CARD11 • DNMT3A • FAT2 • IGH • JAK2 • NCOR2 • NFKBIE • NOTCH1 • SF3B1 • SMARCA2 • STAT3 • TET2 • TNFRSF14 • TP53 • TSC2 • ZFP36 • ZFP36L1

Discrete Event Simulation and Treatment Sequencing Cost-Effectiveness Model in Second-Line Highly Active Relapse Remitting Multiple Sclerosis for a NICE Multiple Technology Appraisal (ISPOR-EU 2025) - "OBJECTIVES: We undertook a Multiple Technology Assessment (MTA) for the UK National Institute for Health and Care Excellence (NICE) assessing the cost-effectiveness of natalizumab as second line treatment for Highly Active Relapsing Remitting Multiple Sclerosis (HARRMS) in comparison to cladribine, ofatumumab, ocrelizumab and ublituximab... This was the first NICE MTA to use a DES model built in R and it was found to be robust for decision making. In HARRMS, natalizumab biosimilar was found to have greater INMB than originator but cladribine had greatest INMB. The 95% CrI were wide and decision uncertainty, driven by treatment effects, was high."

Clinical • Cost effectiveness • HEOR • CNS Disorders • Multiple Sclerosis

Assessing the Socioeconomic Value of Ocrelizumab Subcutaneous for Treating Relapsing Multiple Sclerosis in the Evolving Treatment Landscape in the United Kingdom (ISPOR-EU 2025) - "Indirect costs included productivity losses to patients (due to short term absence, long term absence and early retirement) and informal care. The socioeconomic value of ocrelizumab subcutaneous versus ublituximab and ofatumumab was approximately £188 million and £44 million, respectively... The results presented show that reducing MS progression can result in patients going back to work and requiring less informal care. This analysis highlights the importance of considering the societal perspective when assessing the benefit of anti-CD20 medicines in RMS to the wider society."

CNS Disorders • Multiple Sclerosis

Multiple sclerosis pathophysiology: a comprehensive review of genetic, environmental, and immunological drivers. (PubMed, Inflammopharmacology) - "Therapeutically, modern disease-modifying therapies (interferon-β, glatiramer acetate, oral S1P modulators, fumarates, teriflunomide, cladribine, natalizumab, anti-CD20 monoclonals including ocrelizumab, ofatumumab, and ublituximab) reduce relapse rates and MRI activity yet do not consistently prevent disability progression-particularly in non-active progressive MS. Acute relapses are treated with high-dose corticosteroids; plasma exchange is reserved for steroid-refractory attacks. These realities motivate mechanism-informed strategies that pair sustained immune control with CNS-intrinsic neuroprotection and remyelination."

Journal • Review • CNS Disorders • Epstein-Barr Virus Infections • Immunology • Infectious Disease • Inflammation • Multiple Sclerosis • HLA-DRB1 • IFNB1

Ublituximab (Briumvi) for Early Forms of Relapsing Multiple Sclerosis (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Northwestern University

New P4 trial • CNS Disorders • Multiple Sclerosis • Plasma NfL

TG Therapeutics Reports Third Quarter 2025 Financial Results and Raises BRIUMVI Revenue Guidance (TG Therapeutics Press Release) - "BRIUMVI U.S. net product revenue of $152.9 million for the third quarter of 2025, representing 84% growth over the same period in 2024 and 10% growth over Q2 2025...Raises total global revenue target to approximately $600 million for the full year 2025 (prior guidance of $585 million for full year 2025)."

Sales • Multiple Sclerosis

Real-World Perspectives on Switching Patients with Multiple Sclerosis from Anti-CD20 Therapy to Cladribine Tablets from USA-Based Advanced Practice Providers: A Podcast. (PubMed, Adv Ther) - "The discussion builds on the results from a real-world retrospective survey of 100 HCPs aimed at understanding their rationale for transitioning patients from anti-CD20 therapies (e.g., ocrelizumab, ofatumumab, rituximab, ublituximab) to CladT...This podcast also highlights the economic benefits of CladT, the role of SDM, and recommendations based on clinical experiences. Podcast Transcript (MP4 217843 kb)."

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

TG Therapeutics Completes Enrollment in the Phase 3 ENHANCE Trial Evaluating its New Simplified Dosing Schedule for BRIUMVI (GlobeNewswire) - "The primary endpoint of this trial is non inferior exposure with respect to area under the curve (AUC) at week 16...'We remain deeply committed to continuing to enhance the overall patient experience with BRIUMVI, and if the data are positive, this new dosing regimen could be ready for launch in 2027.'"

Clinical • Enrollment closed • Multiple Sclerosis

Study to Assess Effects of Ublituximab in Pediatric Participants With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2/3 | N=240 | Not yet recruiting | Sponsor: TG Therapeutics, Inc.

New P2/3 trial • CNS Disorders • Multiple Sclerosis • Pediatrics

Real-world safety assessment of ublituximab: a pharmacovigilance analysis based on the FDA adverse event reporting system. (PubMed, Int J Clin Pharm) - "This study provided preliminary insights into the post-marketing safety profile of ublituximab by confirming its known AEs and investigating unexpected AEs. These findings contribute to evidence-based risk minimization strategies and pharmacovigilance activities for ublituximab in clinical practice."

Adverse events • Clinical • Journal • Real-world evidence • Alopecia • CNS Disorders • Immunology • Infectious Disease • Multiple Sclerosis • Nephrology • Pain • Respiratory Diseases

Efficacy and safety of ublituximab for relapsing multiple sclerosis patients: current evidence and expert opinion. (PubMed, J Neurol) - "Phase III randomized controlled trials ULTIMATE I and II confirmed superior efficacy of ublituximab over teriflunomide, achieving substantial reductions in annualized relapse rates, near-complete suppression of gadolinium-enhancing T1 lesions and new/enlarging T2-hyperintense white matter lesions, as well as higher rates of no evidence of disease activity 3. Real-world evidence, extended follow-ups, and comprehensive biomarker assessment specific to MS-related pathology will be essential to confirm its efficacy and optimize RMS patients' management. This review synthesizes discussions from two meetings of Italian Neurologists held in 2024 and 2025, focusing on efficacy and safety data of ublituximab, and providing a comprehensive and in-depth analysis of its current and future role in RMS treatment."

Journal • Review • CNS Disorders • Multiple Sclerosis

Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 monoclonal antibodies: a systematic review and meta-analysis of observational studies. (PubMed, Expert Opin Drug Saf) - "Overall, rituximab exhibited a higher prevalence of hypogammaglobulinemia [11%; 95% Confidence Interval (CI): 0.08 to 0.15], infections of any grade (25%; 95%CI: 0.18 to 0.32), genito-urinary infections (9%;95%CI: 0.05 to 0.12), while ocrelizumab exhibited a higher prevalence of serious infections (6%; 95%CI: 0.03 to 0.09) and respiratory infections (12%; 95%CI: 0.07 to 0.17). The paucity of data for ofatumumab and ublituximab highlights a research gap...The quality of included studies was mainly classified as poor. Monitoring and educating patients on anti-CD20 mAb is fundamental to quickly identifying adverse events and minimizing clinical risks.PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42024617575."

Journal • Observational data • Retrospective data • Review • CNS Disorders • Infectious Disease • Multiple Sclerosis • Respiratory Diseases • Urology

A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Radiological and Clinical Effects of Subcutaneous Ublituximab in Participants With Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: TG Therapeutics, Inc.

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

Exploration of Novel Imaging Biomarkers on OCT for Ublituximab Treatment Response in Multiple Sclerosis (clinicaltrials.gov) - P=N/A | N=30 | Not yet recruiting | Sponsor: University of Maryland, Baltimore | Initiation date: Jun 2025 ➔ Jan 2026

Biomarker • Trial initiation date • CNS Disorders • Multiple Sclerosis

Complications of Multiple Sclerosis Disease-Modifying Therapies in the Southeastern United States: Anti-CD20 Therapy is Associated with Higher Rates of Emergency Department Visits due to Infections (ECTRIMS 2025) - "Introduction: The anti-CD20 therapies rituximab (RTX), ocrelizumab (OCR), ofatumumab (OFA), and ublituximab (UTX) are considered highly effective disease modifying therapy (DMT) in relapsing-remitting multiple sclerosis (MS)...Objectives/Aims: To assess rates of emergency department (ED) visits due to infection in people with MS (PwMS) treated with anti-CD20 therapy compared to glatiramer acetate (GA)... This large cohort provides evidence that PwMS treated with anti-CD20 therapy have higher rates of ED visits due to infections compared to GA. Disclousure of interest: Freddy Escobar-Montalegre: nothing to disclose. Ziyad Aboudan: nothing to disclose."

Late-breaking abstract • CNS Disorders • Dermatology • Infectious Disease • Multiple Sclerosis • Nephrology • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Ublituximab use in a Real-World Setting: Rapid CD19+ B-Cell Depletion and Comprehensive Clinical Evaluation Beyond EDSS (ECTRIMS 2025) - "This study provides the first Italian real-world experience with Ublituximab, including immunological profiling of CD19+ B-cell depletion following the initial infusion. Moreover further validation in larger cohorts is warranted."

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

Real world clinical experience from ENABLE, the first Phase 4 observational study for patients with relapsing multiple sclerosis initiating ublituximab (ECTRIMS 2025) - P | "Among those switching to ublituximab, 42.2% were from anti-CD20 therapy, 20% from natalizumab, 9.5% from fumarates, 7.7% from other oral therapies, 5.2% from teriflunomide, 5.1% from platform therapies, and 3.4% from alemtuzumab. The real-world cohort from ENABLE represents a slightly older, and more diverse MS population with longer disease duration compared to ULTIMATE I and II. The real-world data from this cohort may aid clinical decision making for patients either initiating ublituximab or transitioning from a prior MS therapy."

Clinical • Observational data • P4 data • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Impact of Anti-CD20 vs Other Disease-Modifying Therapies on Serum Neurofilament Light Chain in MS Patients (ECTRIMS 2025) - "We included studies that compared serum NfL levels in people with MS (PwMS) treated with anti-CD20 therapy (Ocrelizumab [OCR], Rituximab [RTX], Ublituximab [UTX], and Ofatumumab [OFA]) and another DMT in MS...OCR was compared to natalizumab and interferon beta 1A, and OFA was compared to teriflunomide... Anti-CD20 therapy leads to higher decreases in serum NfL levels compared to other MS DMT."

Clinical • CNS Disorders • Multiple Sclerosis • NEFL

Ublituximab as a Treatment Option for Relapsing Multiple Sclerosis Patients with Early B-Cell Repopulation on Ocrelizumab: Case Series (ECTRIMS 2025) - "All three patients demonstrated improved B-cell depletion and clinical stability following the transition, with one patient showing radiological improvement. Ublituximab may improve B-cell depletion when ocrelizumab fails to maintain it between 6-monthly infusions. Larger, diverse studies with extended follow-up are needed to validate these findings and to better understand the clinical significance of EBR."

Clinical • CNS Disorders • Multiple Sclerosis • CD19

Safety and tolerability of a modified ublituximab dosing regimen: Updates from the ENHANCE study (ECTRIMS 2025) - "In the ENHANCE study, a modified ublituximab dosing regimen consolidating the initial 150 mg and 450 mg doses into a single 600 mg infusion and administering 450 mg doses in 30 minutes demonstrated a safety profile that appeared consistent with that seen in the pivotal ULTIMATE I/II Phase 3 trials. The ENHANCE study has been amended to a randomized trial to evaluate the pharmacokinetics, safety, and efficacy of 600 mg doses compared to the approved dosing regimen. Enrollment in ENHANCE is ongoing and additional data will be presented."

Clinical • CNS Disorders • Multiple Sclerosis