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

Switching to ublituximab from prior anti-CD20 monoclonal antibody therapy: a case report series. (PubMed, Front Immunol) - "These cases highlight suboptimal B-cell depletion, inadequate MS disease control, and/or tolerability concerns in people with MS who had clinical improvements or stabilization of disease following a switch from ocrelizumab or rituximab to ublituximab. Within-class switching from a prior anti-CD20 mAb therapy to ublituximab is feasible and may improve outcomes in some people with MS."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis

AAN 2025: Combined first Briumvi dose well tolerated in relapsing MS (Multiple Sclerosis News Today) - P3b | N=300 | ENHANCE (NCT05877963) | Sponsor: TG Therapeutics, Inc. | "A single 600 mg dose of Briumvi (ublituximab-xiiy) - instead of the approved 150 mg initial dose plus a 450 mg dose two weeks later- was well tolerated by adults with relapsing forms of multiple sclerosis (MS). That’s according to new data from the ENHANCE Phase 3b clinical trial (NCT05877963), which is evaluating the safety and efficacy of a modified treatment regimen of Briumvi....Thirty-three participants were deemed depleted as they had less than 10 B-cells/mcl. Most were previously treated with Ocrevus (85%) and the rest with Kesimpta (15%). This group received 600 mg of Briumvi over an hour, with the same second dose regimen as the non-depleted group....In the non-depleted group, 24.3% reported an IRR. Of these, 12.9% were mild (grade 1), 10% were moderate (grade 2), and 1.4% were considered severe (grade 3)."

P3 data • Multiple Sclerosis

The Evolution of Anti-CD20 Treatment for Multiple Sclerosis: Optimization of Antibody Characteristics and Function. (PubMed, CNS Drugs) - "Initial apparent success with rituximab in MS and neuromyelitis optica spurred development of the anti-CD20 monoclonal antibody (mAb) therapies ocrelizumab, ofatumumab, and ublituximab as well as the anti-CD19 mAb inebilizumab...Glycoengineering of the mAbs ublituximab and inebilizumab enhances ADCC and can overcome the reduced responses to mAb-mediated B-cell depletion associated with certain genetic polymorphisms. Other strategies for therapeutic targeting of CD20, including brain shuttle antibodies (e.g., RO7121932), bispecific antibodies, chimeric antigen receptor T-cell therapies, and antibody-drug conjugates, are in active clinical development and may be future treatment approaches in MS and other B-cell-mediated autoimmune diseases."

Journal • Review • CNS Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Oncology • Rare Diseases

TG Therapeutics Announces Data Presentations for BRIUMVI in Multiple Sclerosis at the American Academy of Neurology 2025 Annual Meeting (GlobeNewswire) - "TG Therapeutics, Inc...announced the presentation of data yesterday highlighting BRIUMVI (ublituximab-xiiy) in patients with relapsing forms of multiple sclerosis (RMS), at the American Academy of Neurology 2025 annual meeting. Links to each presentation are included below....We are encouraged by the results from the ENHANCE trial presented yesterday, which demonstrated that a single day one 600 mg dose of BRIUMVI was well tolerated."

Clinical data • Multiple Sclerosis

TG Therapeutics Announces Data Presentations for BRIUMVI in Multiple Sclerosis at the American Academy of Neurology 2025 Annual Meeting (GlobeNewswire) - "The results of the retrospective ENAMOR survey, which includes data from approximately 400 individuals across 21 MS centers who have been treated with BRIUMVI in the real-world setting, showed a favorable tolerability profile, including a lower rate of infusion related reactions at the first BRIUMVI dose than was observed in the ULTIMATE Phase 3 trials. Interestingly, approximately 90% of surveyed patients were given acetaminophen as a pre-medication in this real-world setting, whereas it was excluded as a premed as per protocol in the ULTIMATE Phase 3 trials potentially offering a rationale for the lower rate of infusion related reactions observed....We plan to further evaluate the efficacy and tolerability of BRIUMVI in the real world setting through the ENABLE Phase 4 96-week observational study which will enroll approximately 500 patients across approximately 100 MS centers in the United States."

Real-world • Retrospective data • Trial status • Multiple Sclerosis

Newly Launched Phase 4 ENABLE Trial to Test Real-World Efficacy of Ublituximab in Relapsing Multiple Sclerosis (NeurologyLive) - "Investigators have shared the study design of ENABLE, the first phase 4, post-marketing observational trial (NCT06433752) assessing ublituximab (Briumvi; TG Therapeutics), one of the more newly approved medications for relapsing multiple sclerosis that came into market in 2022. The study, which aims to collect data on effectiveness, safety, and tolerability of the therapy, is expected to enroll at least 500 patients with relapsing MS across 100 centers in the United States. Expected to span a total of 96 weeks, this phase 4 study will use annualized relapse rates (ARRs) as the primary end point, with secondary end points that include proportion of patients experiencing adverse events (AEs), as well as incidence, severity, and type of infusion-related reactions (IRRs) at each infusion."

Clinical protocol • Multiple Sclerosis

Idiosyncratic Drug-induced Neutropenia Secondary to Ofatumumab Exposure in Multiple Sclerosis: A Case Report and Analysis of Food and Drug Administration Adverse Event Reporting System (P8-1.012). (PubMed, Neurology) - "Three anti-CD20 mAbs (ocrelizumab, ofatumumab, and ublituximab) are currently approved by the Food and Drug Administration (FDA) for MS treatment...Dr. Hooshmand has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG Therapeutics ."

Adverse events • Journal • Agranulocytosis • CNS Disorders • Dental Disorders • Febrile Neutropenia • Granulocytopenia • Hematological Disorders • Infectious Disease • Multiple Sclerosis • Neutropenia • Pain • Septic Shock

TG Therapeutics Announces Two Publications Highlighting BRIUMVI in Medical Journals (GlobeNewswire) - "The article describes a retrospective case series of seven individuals with multiple sclerosis (MS) treated in private practice or at an MS clinic who switched to ublituximab from a different anti-CD20 monoclonal antibody therapy due to efficacy or tolerability concerns....The article focuses on the unique characteristics of the anti-CD20 monoclonal antibodies used to treat MS that may be relevant to differences in therapeutic efficacy, tolerability, and patient experience—namely, scaffold, mechanism of action (eg, complement-dependent cytotoxicity vs antibody-dependent cellular cytotoxicity), and Fc engineering."

Clinical • Multiple Sclerosis

A Study Evaluating the Effect of BRIUMVI® (Ublituximab) on Pregnancy and Infant Outcomes in Participants With Multiple Sclerosis (MS) (clinicaltrials.gov) - P=N/A | N=728 | Recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Mar 2035 | Trial primary completion date: Jun 2025 ➔ Mar 2035

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

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

A chemotherapy-free regimen of acalabrutinib, umbralisib and ublituximab achieved high response rates and undetectable minimal residual disease in patients with untreated mantle cell lymphoma. (PubMed, Br J Haematol) - No abstract available

Journal • Minimal residual disease • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Inoculating maize (Zea mays L.) seeds with halotolerant rhizobacteria from wild halophytes improves physiological and biochemical responses of seedlings to salt stress. (PubMed, Biol Futur) - "When the maize seeds inoculated with these 19 isolates were grown under normal conditions, four isolates‒TG-4 (Halomonas arcis), TG-8 (Marinococcus tarigensis), TG-12 (Halobacillus dabanensis), and TG-20 (Halomonas eurihalina)-significantly stimulated seedling growth and development...According to the parameters, the results indicated that TG-4, TG-8, and TG-12, in particular, have the potential to function as plant growth-promoting rhizobacteria and effectively enhance salt stress tolerance in the maize seedlings. Overall, this research highlights the potential of halotolerant bacteria to improve salt stress tolerance in maize plants through multifaceted mechanisms, offering valuable insights for sustainable agriculture in saline environments."

Journal

A Phase 1, Multicenter, Single-Arm, Dose-Escalation Study of BMS-986353 (CC-97540), a CD19-Directed Chimeric Antigen Receptor T Cell Therapy Manufactured Using a Next-Generation Process, Evaluating Safety and Tolerability in Patients With Relapsing or Progressive Forms of Multiple Sclerosis (Breakfree-2) (ACTRIMS Forum 2025) - P1 | "BMS-986353 (CC-97540) is an investigational CAR T cell therapy expressing the CD19-directed CAR used in FDA-approved lisocabtagene maraleucel; the NEX-T® manufacturing process shortens manufacturing time and optimizes phenotypic attributes...Two to 9 days after lymphodepletion (3 days of fludarabine and cyclophosphamide), a single BMS-986353 infusion was administered...One pt was a 33-yr-old male diagnosed with RRMS in 2011 with an Expanded Disability Status Scale (EDSS) score at screening of 3.0, whose previous MS treatments included alemtuzumab, glatiramer acetate, interferon beta-1a, fingolimod, natalizumab, ocrelizumab, ofatumumab, and ublituximab... Treatment with BMS-986353 demonstrated promising initial safety in pts with highly active RRMS, with no ICANS observed and 1 pt with transient low-grade CRS. Trial enrollment is ongoing. Updated safety, pharmacokinetic, and translational data will be presented."

CAR T-Cell Therapy • Clinical • P1 data • CNS Disorders • Hematological Disorders • Infectious Disease • Inflammation • Multiple Sclerosis • Neutropenia • Thrombocytopenia • CD19

TG Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "2025 Development Pipeline Anticipated Milestones: Commence pivotal program of subcutaneous ublituximab; Commence a pivotal program based on data from the ENHANCE trial with the goal of enhancing the patient experience on intravenous BRIUMVI; Enroll participants into the ongoing trial evaluating BRIUMVI in autoimmune diseases outside of MS; Enroll participants into the Phase 1 azer-cel trial in autoimmune disease, beginning with progressive forms of MS; Present updated data at major medical conferences throughout the year."

Clinical data • Enrollment status • New trial • Immunology • Multiple Sclerosis

Efficacy and Safety of a Modified Ublituximab Regimen (ENHANCE) (AAN 2025) - "Consolidating the Day 1 (150 mg) and Day 15 (450 mg) ublituximab doses into a single 600 mg infusion administered on Day 1 eliminates the need for repeated visits within the first two weeks of initiating treatment and consequently reduces patient burden. Enrollment in ENHANCE is ongoing and full data for this modified regimen will be presented."

Clinical • CNS Disorders • Multiple Sclerosis

Retrospective Analysis of CD20-Directed Cytolytic Antibody Treatment Switches to Ozanimod in Patients with Relapsing Multiple Sclerosis (MS) (ACTRIMS Forum 2025) - "To assess the rationale and methodology for cessation of a CD20-directed cytolytic antibody therapy (ocrelizumab, ofatumumab, rituximab, or ublituximab), who later transitioned to ozanimod.2... Switching from a CD20-directed cytolytic antibody therapy to ozanimod was driven by patient preference, recurrent infections, and physical/cognitive disability progression. Patient preference, desire to be on an oral medication, and perception that patients may experience less infections were top reasons for transitioning to ozanimod. Most patients transitioned in less than 4 months (IV formulation) and in less than 3 months (SC formulation), with 92% experiencing no adverse events."

Retrospective data • CNS Disorders • Cognitive Disorders • Developmental Disorders • Infectious Disease • Multiple Sclerosis • Pain • Respiratory Diseases • CD20

Retrospective Evaluation of Infusion Tolerability: Ublituximab Real-world Observational Survey (ENAMOR) (AAN 2025) - "Data from the ENAMOR survey supports that ublituximab infusions are well tolerated in the real-world clinical practice setting. Additional data to be presented at the meeting."

Real-world • Real-world evidence • Retrospective data • CNS Disorders • Multiple Sclerosis

Five Years of Ublituximab in Relapsing Multiple Sclerosis: Additional Results from Open-label Extension of ULTIMATE I and II Studies (AAN 2025) - "Objective:To evaluate the long-term clinical efficacy and safety of ublituximab.Background:In ULTIMATE I and II studies, ublituximab (UBL) demonstrated significant reduction in disease activity vs. teriflunomide (TER) over 2 years. UBL treatment for 5 years provided MS patients with sustained clinical benefit versus switching after 2 years of TER, with 1 relapse every 50 years of treatment, and significant benefits on disability progression. Results confirm early UBL initiation confers long-term benefits."

Clinical • CNS Disorders • Multiple Sclerosis

Safety and Tolerability of 30-minute Ublituximab Infusions: Updates from the ENHANCE Study (ACTRIMS Forum 2025) - "29 participants transitioned from ocrelizumab, of which 51.7% (15/29) reported wearing off effect. Administration of a full 450 mg dose in 1 hour on Day 1 was well tolerated in B-cell depleted patients transitioning from prior anti-CD20 therapy. Further, the frequency of IRRs observed during the 30-minute infusion at Week 24 was low and establishes feasibility of rapid infusions that may offer improved convenience. Enrollment in ENHANCE is ongoing and additional data will be presented."

Clinical • CNS Disorders • Multiple Sclerosis

A Novel MS Disability Metric (KHSFSS) Sensitively Demonstrates Disability and MS Quality of Life (QOL) Improvement with High Temporal Resolution in Ultimate I/II Trial (ACTRIMS Forum 2025) - P3 | "For these reasons, additional metrics for measuring meaningful changes in disability are needed.Objectives: Demonstrate use of KHSFSS in Phase 3 trial data. EDSS and QOL data from the Phase 3 ULTIMATE I/II studies (NCT03277261/48) evaluating ublituximab (UBL) vs. teriflunomide (TER) in relapsing MS were analyzed post-hoc. KHSFSS, derived from prospectively collected EDSS instruments, showed sensitive, rapid, meaningful, and sustained clinical improvements of disability in UBL over TER, dramatic in a minority and significant in a substantial fraction of UBL subjects. The KHSFSS improvers also improved QOL greater in UBL subjects."

HEOR • Infectious Disease • 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

Biomarker • New trial • CNS Disorders • Multiple Sclerosis

Idiosyncratic Drug–induced Neutropenia Secondary to Ofatumumab Exposure in Multiple Sclerosis: A Case Report and Analysis of Food and Drug Administration Adverse Event Reporting System (AAN 2025) - "Three anti-CD20 mAbs (ocrelizumab, ofatumumab, and ublituximab) are currently approved by the Food and Drug Administration (FDA) for MS treatment...IDIN is a rare but potentially life-threatening complication of anti-CD20 mAbs. Although FDA prescribing information does not currently indicate neutropenia as a risk for ofatumumab, it is documented in the FAERS database. Early signs of neutropenia, such as viral symptoms and mouth sores should prompt testing for neutrophil count."

Adverse events • Case report • Clinical • Agranulocytosis • CNS Disorders • Dental Disorders • Febrile Neutropenia • Granulocytopenia • Hematological Disorders • Infectious Disease • Multiple Sclerosis • Neutropenia • Pain • Septic Shock

ENHANCE: Study to Evaluate Efficacy of a Modified Regimen of Ublituximab (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

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

ENABLE: The First Phase 4 Observational Study for Patients with Relapsing MS Treated with Ublituximab in Real World Clinical Setting (AAN 2025) - P | "Objective:To evaluate the real-world clinical effectiveness, safety, and tolerability of ublituximab.Background:Ublituximab, approved for treating relapsing multiple sclerosis (RMS), has demonstrated significant clinical benefits vs teriflunomide in two identical phase 3 trials, ULTIMATE I and II. ENABLE will provide valuable real-world clinical evidence on the effectiveness, safety, and tolerability of ublituximab from MS centers across the US."

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

Clinical Implications of a Multiple Sclerosis and Neurosarcoidosis Overlap (ACTRIMS Forum 2025) - "All patients (N=5) were eventually placed on disease modifying therapy (DMT) for maintenance therapy (Ofatumumab N=2, Ocrelizumab N=1, Ublituximab N=1, and Teriflunomide N=1). In our case series of patients with biopsy-confirmed sarcoidosis with potential MS/neurosarcoidosis overlap, multidisciplinary decision-making favored CD20-targeted B-cell depletion, with favorable outcomes and the potential to treat both conditions."

Clinical • CNS Disorders • Immunology • Multiple Sclerosis • Sarcoidosis