Ublituximab, Now Briumvi, Approved in US for Relapsing Forms of MS
The anti-CD20 therapy is expected to launch in Q1 2023, says TG Therapeutics
The U.S. Food and Drug Administration has approved TG Therapeutics‘ B-cell-depleting therapy ublituximab under the brand name Briumvi for the treatment of adults with relapsing forms of multiple sclerosis (MS), the company announced.
The approval covers clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS). TG Therapeutics plans to launch the therapy in the U.S. in the first quarter of 2023.
A decision was initially expected by Sept. 28, but TG Therapeutics’ submission of more clinical information in response to an FDA request was deemed a major amendment to the application, warranting additional review time and pushing the decision date to Dec. 28.
“Today’s FDA approval marks an exciting day for everyone touched by MS and everyone that has worked on the development of Briumvi. We believe in the importance of treatment alternatives for patients and believe the profile of Briumvi offers unique attributes to patients and physicians alike,” Michael S. Weiss, TG Therapeutics’ chairman and CEO, said in a company press release.
Briumvi is an antibody-based therapy designed to kill B-cells, a type of immune cell implicated in the autoimmune attacks that drive MS. It does so by targeting the CD20 protein found at the surface of B-cells.
The treatment now joins Roche’s Ocrevus (ocrelizumab) and Novartis’ Kesimpta (ofatumumab) as the third anti-CD20 therapy approved for MS. According to TG Therapeutics, as of the third quarter of 2022, about 50% of MS patients starting a new therapy use an anti-CD20 treatment.
Delivered as an hourlong intravenous (into-the-vein) infusion once every six months, Briumvi was engineered to be more potent than other anti-CD20 therapies, allowing for lower doses and shorter infusion times.
“This approval is great news for patients living with MS and provides an appealing treatment alternative that can be administered in a one-hour infusion twice-a-year following the starting dose, which I believe is an added benefit to patients,” said Lawrence Steinman, MD, Zimmermann professor of neurology & neurological sciences, and pediatrics at Stanford University.
Briumvi’s approval was backed by pooled data from twin Phase 3 clinical trials, ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248), which evaluated Briumvi against Sanofi Genzyme’s approved oral MS treatment Aubagio (teriflunomide).
The trials collectively enrolled 1,094 adults with active relapsing types of MS — 98% of whom had RRMS and 2% active SPMS — who were randomly assigned to receive Briumvi or Aubagio for 96 weeks, or almost two years.
Briumvi was administered as an intravenous infusion on the first day of treatment (150 mg administered in four hours), followed by a 450 mg infusion on day 15 (administered in one hour), and every six months thereafter (administered in one hour). Aubagio was given as daily 14 mg oral tablets.
Published trial data showed that, compared with Aubagio, Briumvi significantly lowered patients’ annualized relapse rate by about 59% in the ULTIMATE I study and by 49% in ULTIMATE II, meeting the trials’ main goal. It was also associated with significant reductions in the number of inflammatory lesions (by about 97%), and of new or enlarging brain lesions (by at least 90%).
A number of post-hoc trial analyses, or those carried out after the trial was completed, continued to demonstrate the clinical benefits of Briumvi, including gains in other disability-related measures and quality of life.
Analyses also showed that Briumvi-treated patients were significantly more likely to achieve a 12-week confirmed disability improvement — an easing of disability sustained for at least three months — compared with those on Aubagio.
Moreover, a significantly greater proportion of patients in the Briumvi group, compared with those receiving Aubagio, (44.6% vs. 12.4%) achieved no evidence of disease activity (NEDA-3) — a three-parameter milestone defined as the complete absence of relapses, new lesions, or disability worsening — over the 96-week trial.
Briumvi was also associated with more participants achieving NEDA-4, which is similar to NEDA-3 but includes a fourth parameter related to brain shrinkage.
Benefits of the treatment were similar among key patients subgroups. Briumvi generally continued to outperform Aubagio on key efficacy measures when patients were divided by sex, age, disability, number of relapses prior to treatment, treatment history, or inflammatory lesion burden at the study’s start.
“Over the past several years we have seen a dramatic shift in the MS treatment landscape towards the use of B-cell therapy, which has shown to be highly effective in reducing relapses in patients,” said Steinman, who led the ULTIMATE trials. “The outcome of the ULTIMATE I & II trials evaluating ublituximab … represents an important milestone in the history of MS research as the first Phase 3 study of an anti-CD20 monoclonal antibody in patients with relapsing MS to produce an annualized relapse rate of less than 0.10, which translates to less than 1 relapse in 10 years.”
In terms of safety, Briumvi had a generally good safety profile in clinical testing. The most common side effects reported among patients given the therapy in the ULTIMATE trials were infusion-related reactions, respiratory tract infections, herpes virus-associated infections, pain, insomnia, and fatigue.
“We are pleased to have a new treatment approved for people with relapsing forms of multiple sclerosis,” said Bari Talente, executive vice president, advocacy and healthcare access, at the National MS Society. “Since we know that early treatment can minimize disease progression, it is incredibly important for people with MS to have a choice of treatment options to find the one that works best for them.”
TG Therapeutics offers a Briumvi Patient Support program to help patients gain access to the therapy. Information on insurance coverage, financial assistance (including copay programs), and support in preparing for treatment infusion will be provided.
“The availability of anti-CD20s has launched a new era of high efficacy therapies for multiple sclerosis,” said June Halper, CEO of the Consortium of Multiple Sclerosis Centers. “The approval of Briumvi is wonderful news. … The addition of Briumvi has added to the hope chest of patients, families, and the MS professional community.”
No details on Briumvi’s pricing have been confirmed yet. TG Therapeutics also has filed for ublituximab’s approval in the European Union.