Ublituximab, an investigational anti-CD20 antibody, outperformed Aubagio (teriflunomide) in lowering the frequency of relapses among people with active, relapsing forms of multiple sclerosis (MS), according to top-line data from the Phase 3 ULTIMATE trials.
Full results, including data on safety and secondary goals, are expected to be presented at a medical congress in the first half of 2021. The positive findings are also meant to support a biologics license application submission to the U.S. Food and Drug Designation (FDA) seeking the therapy’s approval by mid-year 2021.
“We are so pleased to share these positive top-line results for our ULTIMATE MS studies,” Michael S. Weiss, executive chairman and CEO of the treatment’s developer, TG Therapeutics, said in a press release. “If approved, ublituximab has the potential to offer patients a one-hour infusion [every six months], which we believe will be an attractive option for many patients with MS.”
Ublituximab is an antibody that works by targeting CD20, a protein found on the surface of B-cells, a type of immune cell known to drive the inflammation that causes nervous system damage in MS.
Being tested also as a potential treatment for B-cell cancers, ublituximab was specifically designed to maximize B-cell death by triggering several cell death-inducing immune responses, particularly antibody-dependent cellular cytotoxicity.
As such, the therapy, administered directly into the bloodstream, is said by the company to have superior potency compared with current anti-CD20 antibodies, allowing for the use of lower doses and shorter infusion times.
“B-cell targeted therapy with anti-CD20 monoclonal antibodies has dramatically shifted the treatment paradigm for patients with MS and has shown to be very effective in reducing relapses in patients,” Lawrence Steinman, MD, Zimmermann professor of neurology and neurological sciences, and pediatrics at Stanford University, who led both ULTIMATE trials.
The ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) studies evaluated the safety and effectiveness of ublituximab against Sanofi Genzyme’s Aubagio in a total of 1,094 adults with active, relapsing forms of MS.
Aubagio is an approved oral treatment for relapsing MS that is thought to work by decreasing the activity of immune cells, namely B-cells and T-cells.
Participants, recruited at clinical sites across 10 countries, had a median age of 35–36 years, and most (98%–98.3%) had a diagnosis of relapsing-remitting MS, while up to 2% had secondary progressive MS. They were randomly assigned to receive either a rapid, one-hour infusion of ublituximab (450 mg) every six months or a daily oral tablet of Aubagio (14 mg) for 96 weeks (nearly two years).
Of note, patients in the ublituximab group were given a four-hour infusion of 150 mg on day one and a one-hour infusion of 450 mg on day 15, before starting the every-six-month regimen.
The main goal of both trials was to assess whether ublituximab was superior to Aubagio at dropping patients’ annualized relapse rates (ARR), or the number of relapses per year. Secondary goals included assessing changes in brain lesions on MRI scans, and time to confirmed disability progression.
Newly announced top-line results showed that both trials met their main goal, with ublituximab treatment resulting in a significant drop in AAR — a relative reduction of 60% in ULTIMATE 1 and of 50% in ULTIMATE 2 — compared with Aubagio.
Notably, ublituximab-treated patients had a very low adjusted ARR — less than 0.10 relapses per year.
“I am pleased to see such positive results from this important trial exploring a one-hour infusion of ublituximab every six months,” Steinman said. “If approved, the unique attributes of ublituximab, particularly that it has been glycoengineered for enhanced antibody dependent cellular cytotoxicity, may offer benefits to patients in the [relapsing] MS treatment paradigm.”
The ULTIMATE studies were conducted under the FDA’s special protocol assessment, which allows sponsor companies to meet with the agency to determine the best design and size of clinical trials to support a potential marketing approval.
“We want to thank the patients, caregivers, doctors and research teams who participated in these studies, as well as the TG team for their efforts in helping to achieve this important milestone,” Weiss said. “We look forward to [completing the biologics license application] submission targeted for mid-next year.”
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