October 19, 2021 News by Marisa Wexler, MS #ECTRIMS2021 ā CD20-positive T-cells May Be Early Drivers of MS Editorās note: TheĀ Multiple Sclerosis News Today team is providing in-depth coverage of the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 13ā15. GoĀ here to see the latest stories from the conference. Certain types of…
June 23, 2021 News by Marisa Wexler, MS Long-term Kesimpta Use Not Seen in Trial to Depress Antibody Levels Long-term use ofĀ Kesimpta (ofatumumab) among people with multiple sclerosis (MS) did not substantially lower their antibody levels, allowing them to retain an ability to fight infections, new data from a Phase 3 clinical trial indicate. “These long-term results continue to support Kesimpta as a high-efficacy, first-choice treatment with…
May 3, 2021 Columns by Ed Tobias MS News That Caught My Eye Last Week: FDA and Tysabri, COVID-19 and CD20, Gilenya Infections, Therapeutic Lag FDA Rejects Under-the-skin Tysabri for Relapsing MS I expect this decision will be a disappointment for those who had hoped to be able to self-administer highly effective Tysabri as a shot rather than an IV infusion. But I switched from Avonex to Tysabri, because after a few years of…
January 19, 2021 News by Marta Figueiredo, PhD Ocrevus Targets Pro-inflammatory T-cells, Not Just B-cells, in PPMS, Study Finds In addition to significantly reducing subsets of B-cells ā its main immune cell target ā Ocrevus (ocrelizumab) lessens pro-inflammatory immune T-cells in people with primary progressiveĀ multiple sclerosis (PPMS), a small study shows. Notably, the suppression of immune cell subsets thought to be involved in the abnormal immune responses…
September 30, 2020 News by Joana Carvalho, PhD #MSVirtual2020 – Rituximab, Ocrevus Linked to Higher Risk of Worse COVID-19 Outcomes The use of certain disease-modifying therapies (DMTs) such asĀ rituximabĀ andĀ Ocrevus (ocrelizumab), which lower the number of a patient’s immune B-cells,Ā may increase the odds of developing a more severeĀ COVID-19 disease course for people withĀ multiple sclerosis (MS), a study suggests. The study, which includes data from the…
June 4, 2020 News by Marisa Wexler, MS FDA Extends Review of Ofatumumab for Relapsing MS to September The U.S. Food and Drug Administration (FDA) is extending its review of Novartis‘Ā ofatumumab, a possible self-administered injection therapy for relapsingĀ multiple sclerosis (MS), the company announced. Originally expected in June, the FDA decision is now expected in September. “Novartis will continue to work with the FDA to…
March 13, 2020 News by Marta Figueiredo, PhD #ACTRIMS2020 – Ofatumumab Self-injection Pen May Be ‘Very Attractive’ Option for Relapsing MS Monthly under-the-skin injections of NovartisāĀ investigational candidate ofatumumab show promise as a convenient, effective, and safe therapeutic option for people with relapsing multiple sclerosisĀ (MS). Data from the ASCLEPIOS and APLIOS clinical trials showed that ofatumumab ā currently under regulatory review for possible approval in the U.S. and Europe…
September 18, 2019 News by Patricia Inacio, PhD #ECTRIMS2019 – Data Shows Ublituximab’s Long-term Safety in Relapsing MS, TG Therapeutics Announced Ublituximab continues to be safe and well-tolerated by people with relapsing forms of multiple sclerosis (MS) after a median follow-up of 124.7 weeks ā more than 2 years ā according to data from an extension Phase 2 trial. The data were shown in a…
June 20, 2019 News by Marisa Wexler, MS Potential Mechanism Behind Effectiveness of B-cell Depletion Therapy in MS Uncovered The loss of immune B-cells, and the resulting changes in the profile of immune T-cells, is a major mechanism of action for the beneficial effects seen with ublituximab treatment in multiple sclerosis (MS) patients, a study suggests. B-cells are a type of immune cell best known for producing…
January 15, 2019 News by Jose Marques Lopes, PhD Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, āOcrelizumab Depletes CD20+Ā T Cells in Multiple Sclerosis Patients,ā was published in the journal Cells. AutoreactiveĀ immune T-cells, which attack the bodyās own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy isĀ Genentechās Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid ā the liquid surrounding the brain and spinal cord ā and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximabĀ (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatmentĀ that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximabās clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical SchoolĀ in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patientsā peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease forĀ a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes ā white blood cells that include T- and B-cells ā and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cellsā fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. āOur results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,ā the researchers wrote. āThese findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,ā they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.
June 5, 2018 News by Patricia Inacio, PhD #CMSC2018 – New Phase 2 Data Supports Ublituximab in Effectively Lowering Relapses, Depleting B-cells in MS Patients New results from a Phase 2 trial evaluating TG Therapeuticsā ublituximab continue to support the therapy’s efficacy in treating relapsing forms of multiple sclerosis (MS). This investigative infusion therapy is now moving into a Phase 3 study. Treatment with 450 mg of ublituximab delivered intravenously in a rapid fashion…
September 19, 2017 News by Patricia Silva, PhD TG Therapeutics Recruiting Patients for Two Phase 3 Trials of Relapsing MS Therapy TG-1101 TG TherapeuticsĀ is recruiting participants for two Phase 3 clinical trials that will evaluate the safety and effectiveness of TG-1101 (ublituximab)Ā as a treatment for relapsing forms of multiple sclerosis. ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) will compare TG-1101, aĀ glycoengineered monoclonal antibody, with Genzyme’sĀ Aubagio…
August 8, 2017 News by Patricia Silva, PhD TG Therapeutics, FDA Agree on Phase 3 Program to Evaluate Relapsing MS Therapy TG-1101 TG TherapeuticsĀ and the U.S. Food and Drug Administration (FDA) have agreed on a special protocol assessment for a Phase 3 trial program evaluating TG-1101 (ublituximab)Ā to potentially treatĀ relapsing forms of multiple sclerosis (MS). A special protocol assessment (SPA) is a procedure by which the agency officially evaluates the…
June 28, 2017 News by Patricia Silva, PhD In Ongoing Phase 2 Trial, Ublituximab Seen to Effectively and Safely Deplete B-cells TG Therapeutics’ investigational treatment āĀ ublituximab (TG-1101)Ā ā led toĀ a near total depletion of B-cells in patients with relapsing forms of multiple sclerosis (MS) taking part inĀ an ongoing Phase 2 trial, the company recently announced. In addition, the company said that ublituximabĀ hadĀ anĀ infusion time as short as one hour,Ā without excessive side…
March 28, 2017 News by Patricia Silva, PhD FDA Approves Ocrevus as 1st MS Treatment for Both Relapsing and Primary Progressive Forms At long last, and for the first time in medical history, peopleĀ with both relapsing and primary progressive forms of multiple sclerosis have reason to celebrate. The U.S. Food and Drug Administration (FDA) today approved Ocrevus (ocrelizumab)Ā as a disease-modifying therapy for both forms of MS, aĀ chronic autoimmune disease.
March 28, 2017 News by Patricia Silva, PhD Ocrevus’ Journey from Defiant Idea to Game-Changing Treatment Twenty years ago, the idea that B-cell depletion could treat multiple sclerosisĀ would have been greeted with a hearty laughĀ byĀ any well-respected neurologist or MS researcher ā or perhapsĀ a scoff. But times change and research advances. Today, a medicine that gets rid of certain B-cells may beĀ the most powerful drug yetĀ developed against…
January 12, 2017 News by Patricia Silva, PhD TG Therapeuticsā B-cell Therapy Could Allow for Rapid Dosing, Early Data Suggest Early data fromĀ TG Therapeutics’ Phase 2 trial of its B-cell-targeting experimental multiple sclerosis (MS) treatment ublituximab (TG-1101), showed that the drugĀ is well-tolerated and effectively reduces B-cells in the blood. MS therapies that deplete B-cells have been effective in relapsing and progressive forms of MS. Like other B-cell-targeting drugs in…
July 21, 2016 News by InĆŖs Martins, PhD Study of Potential Therapy for Relapsing MS That Targets B-Cells Now Recruiting Patients in US Patients with relapsing multiple sclerosis (MS)Ā are being recruited forĀ aĀ clinical trial evaluatingĀ an experimental monoclonal antibody called ublituximab, the National MS Society announced in a recentĀ newsĀ release. The study, being conducted at seven U.S. sites, will enroll at least 24 patients, but this number can go up to 100. MSĀ is considered to be…
June 29, 2016 News by InĆŖs Martins, PhD 1st Potential Therapy for Primary Progressive MS, Ocrelizumab, Under Priority Review by FDA The U.S. Food and Drug Administration (FDA) is givingĀ priority review to a request to approveĀ Ocrevus (ocrelizumab) as a treatment forĀ both forms of multiple sclerosis, the drug’s developer,Ā Genentech, announced. If the company’s Biologics License Application (BLA) is approved,Ā Ocrevus will become the first drug ableĀ to treat patients with either relapsing or…