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

2025 Remaining Pipeline Development Goals (GlobeNewswire) - "Commence patient enrollment into the Phase 3 pivotal program for subcutaneous BRIUMVI; Continue enrollment into the Phase 3 pivotal program based on the streamlined dosing regimens evaluated in the ENHANCE trial, evaluating a single Day 1 600 mg IV dose of BRIUMVI; Continue enrollment of participants into the ongoing clinical trial evaluating BRIUMVI in Myasthenia Gravis (MG); Continue enrollment of participants into the Phase 1 clinical trial evaluating azer-cel for the treatment of autoimmune diseases, beginning with progressive forms of MS; Present updated data at major medical conferences throughout the year."

Clinical data • Enrollment status • Immunology • Multiple Sclerosis • Myasthenia Gravis

SUMMIT: Ublituximab in Autoantibody Positive Immune Mediated Necrotizing Myopathy (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P2 trial • Immunology • Myositis

TG Therapeutics Reports Second Quarter 2025 Financial Results and Raises BRIUMVI Revenue Guidance (GlobeNewswire) - "BRIUMVI U.S. net product revenue of $138.8 million for the second quarter of 2025, representing 91% growth over the same period last year and 16% growth over Q1 2025...Raises BRIUMVI U.S. net product revenue target to $570 - $575 million for the full year 2025 (prior guidance of $560 million for full year 2025); Raises total global revenue target to approximately $585 million for the full year 2025 (prior guidance of $575 million for full year 2025)."

Sales • Immunology • Multiple Sclerosis

Neutropenia Associated With B Cell-Depleting Therapies in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "This study is comprehensive and reflects a large cohort, examining incidence rates of neutropenia with BCDT in MS and NMOSD. Overall, neutropenia was still rare, occurring at a rate of 0.66 per 100 person-years, and infections were associated triggers in some patients. Yet, of relevance to clinicians, neutropenia was not benign: half required hospitalization and 35% experienced recurrence, which is higher than what was reported in clinical trials."

Journal • Retrospective data • CNS Disorders • Hematological Disorders • Infectious Disease • Inflammation • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Neutropenia • Rare Diseases

New treatment for relapsing remitting MS recommended for PBS listing (Multiple Sclerosis Australia) - "The Pharmaceutical Benefits Advisory Committee (PBAC) recommended a new treatment for people with relapsing remitting MS be listed on the Pharmaceutical Benefits Scheme (PBS), following its May 2025 meeting. The treatment, ublituximab (Briumvi), was approved by the Therapeutic Goods Administration (TGA) in June 2025 for treating adults with relapsing remitting MS. While the TGA approves the use of medications in Australia, it is up to the PBAC to recommend whether it should be included on the PBS. Inclusion on the PBS means the medication is subsidised, making it more affordable. The PBAC is required to consider many factors when making recommendations, including the effectiveness and cost of a treatment relative to other available medicines, and the cost to the government of a new listing."

Reimbursement • Multiple Sclerosis

PROVIDE: A Study Evaluating the Presence and Concentration of BRIUMVI™ (Ublituximab) in Breast Milk (clinicaltrials.gov) - P=N/A | N=16 | 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

ENHANCE: Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: TG Therapeutics, Inc. | N=300 ➔ 600

Enrollment change • CNS Disorders • Multiple Sclerosis

TG Therapeutics shares MS drug trial updates (Investing.com) - "TG Therapeutics...has presented new data on its multiple sclerosis drug BRIUMVI (ublituximab-xiiy) at the annual Consortium of Multiple Sclerosis Centers (CMSC) meeting....The data presented came from several sources, including the ULTIMATE I & II Phase 3 trials and the ENHANCE Phase 3b study....One of the presentations, led by Dr. Bruce Cree from the University of California, San Francisco, indicated no association between decreases in serum immunoglobulin levels and serious infections in long-term treatment with BRIUMVI. Another presentation by Dr. Edward Fox of TG Therapeutics discussed the tolerability of the drug in a real-world observational survey. Additionally, Dr. John Foley from Rocky Mountain Multiple Sclerosis in Salt Lake City, Utah, presented updates on the safety and tolerability of 30-minute BRIUMVI infusions."

Clinical data • Multiple Sclerosis

TG Therapeutics Announces Schedule of Data Presentations for BRIUMVI in Multiple Sclerosis at the 2025 Consortium of Multiple Sclerosis Centers Annual Meeting (GlobeNewswire) - "TG Therapeutics, Inc...today announced the upcoming schedule of presentations highlighting BRIUMVI (ublituximab-xiiy) data in patients with relapsing forms of multiple sclerosis (RMS), at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, being held May 28-31, 2025 in Phoenix, Arizona." "

Clinical data • 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

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

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

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

TG Therapeutics Reports First Quarter 2025 Financial Results and Raises BRIUMVI Full Year Revenue Guidance (GlobeNewswire) - "BRIUMVI U.S. net product revenue of $119.7 million for the first quarter of 2025, representing approximately 137% growth over the same period last year...Raises BRIUMVI U.S. net product revenue target to $560 million for the full year 2025 (prior guidance of $525 million for full year 2025); Raises total global revenue target to $575 million for the full year 2025 (prior guidance of $540 million for full year 2025); Second quarter 2025 BRIUMVI U.S. net product revenue target of $135 million Full year 2025 target operating expense of approximately $300 million (excluding non-cash compensation and cost of goods sold)."

Sales • Immunology • Multiple Sclerosis

2025 Development Pipeline Anticipated Milestones (GlobeNewswire) - "Commence pivotal program of subcutaneous BRIUMVI; Commence a pivotal program based on the improved dosing regimens evaluated in the ENHANCE trial, with the goal of enhancing the patient experience on intravenous BRIUMVI; Continue enrollment of participants into the ongoing clinical trial evaluating BRIUMVI in autoimmune diseases outside of MS; Continue enrollment of participants into the Phase 1 clinical trial evaluating azer-cel for the treatment of autoimmune diseases, 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

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

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