#ECTRIMS2021 – Ublituximab Better Than Aubagio at Reducing Disability
Editor’s note: The 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. 13–15. Go here to see the latest stories from the conference.
The investigational anti-CD20 antibody ublituximab outperformed Aubagio (teriflunomide) in reducing disability and slowing brain shrinkage in people with active, relapsing forms of multiple sclerosis (MS), according to new results from the two Phase 3 ULTIMATE clinical trials.
In fact, the rate of brain volume decline or shrinkage was lower with ublituximab in one of the trials, the researchers said.
Both trials were previously shown to meet their main goal and additional efficacy measures, with ublituximab working better than Aubagio at reducing patients’ relapse rates and the number of brain lesions.
The therapy, developed by TG Therapeutics, is now under regulatory review in the U.S. for treating relapsing forms of MS. A similar application is expected to be filed in the European Union.
The new findings were shared by Lawrence Steinman, MD, a professor of neurology at Stanford University, in California, and the global chair for the ULTIMATE studies, at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held virtually Oct. 13-15.
“We are excited to share additional data from the ULTIMATE I & II trials,” which “further elucidate the potential benefits of ublituximab treatment especially on the tertiary [goal] of improvement in MSFC [Multiple Sclerosis Functional Composite] score,” Michael S. Weiss, TG Therapeutics’ chairman and CEO, said in a press release.
Ublituximab is an antibody designed to prevent immune B-cells from triggering the abnormal immune attacks that drive neurodegeneration in MS. It works by targeting CD20, a protein found on B-cells’ surface.
Administered directly into the bloodstream every six months, the therapy is thought to have superior potency relative to current anti-CD20 antibodies — which would allow for lower doses and shorter infusion times. Indeed, the infusion times are about one hour, the shortest to date.
Ublituximab’s two-year safety and effectiveness in people with active, relapsing forms of MS were demonstrated in the identical ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) trials.
These trials tested ublituximab against Sanofi Genzyme’s Aubagio in a total of 1,094 patients from 10 countries. Aubagio is an oral treatment approved for relapsing MS that is thought to work by suppressing the activity of immune cells, namely B-cells and T-cells.
The results showed that ublituximab-treated patients had significantly lower annualized relapse rates (less than 0.1 relapses per year) relative to those given Aubagio, meeting the trials’ main goal.
Ublituximab treatment also was associated with significantly fewer brain lesions, and significantly greater proportions of patients achieving no evidence of disease activity and confirmed disability improvement (less disability), compared with Aubagio.
In the oral presentation, titled “Phase 3 results of the ULTIMATE I & II global studies: ublituximab versus teriflunomide in relapsing multiple sclerosis,” Steinman revealed additional results from the ULTIMATE trials.
One of the analyses assessed changes in the rate of brain volume loss (shrinkage) between six months and two years of treatment. The six-month mark was chosen because, at that point, Aubagio-treated patients had experienced a temporary increase in brain volume relative to the study’s start in both trials.
The results showed that there was no difference in the slopes of brain volume decline between the two groups in ULTIMATE 1, while ublituximab-treated patients had a slower brain shrinkage rate in ULTIMATE 2.
The researchers also looked at changes in the score of the MSFC, assessed at the study start and every three months thereafter.
This validated tool measures three clinical dimensions in MS patients: leg function/walking abilities, through the Timed 25-Foot Walk (T25FW); arm and hand dexterity, using the 9-Hole Peg Test (9-HPT); and cognitive function, with the Paced Auditory Serial Addition Test.
In both trials, two years of treatment with ublituximab was linked to a significant improvement in mean MSFC scores by 76.4–89.6% as compared with Aubagio, indicating greater functionality.
These MSFC findings were further detailed by Steinman in a late-breaking poster, “Ublituximab is associated with significant improvement in the multiple sclerosis functional composite (MSFC): results from the Phase 3 ULTIMATE I & II studies.”
The researchers found that ublituximab-treated patients had significant gains in mean 9-HPT and T25FW scores, indicating better motor function, while patients on Aubagio showed worse upper and lower body performance in both trials.
Notably, group differences in T25FW scores did not reach statistical significance in the ULTIMATE 1 study and cognitive function showed similar improvements in both treatment groups, Steinman noted.
These findings showed that ublituximab was associated with significant improvements in MSFC that were driven by better arm and hand function and walking abilities.
Further analyses of ublituximab’s effects on disability improvement in relapsing MS patients are ongoing, the researchers noted.
Also, the experimental anti-CD20 therapy was generally well-tolerated and linked to similar rates of adverse events as found with Aubagio. The most common adverse events with ublituximab were infusion-related reactions; there were no cases of the rare brain infection progressive multifocal leukoencephalopathy (PML) in either trial.
As expected for a B-cell targeting therapy, ublituximab was associated with a greater proportion of patients showing lower-than-normal levels of immunoglobulin M (IgM) antibodies after two years of treatment, compared with Aubagio.
IgM are the first type of antibody produced by B-cells in response to a threat. Other kinds of antibodies were lower than normal in a similar proportion of patients on ublituximab and Aubagio.
Three patients died, all treated with ublituximab, with a fatal case of pneumonia deemed possibly related to the therapy.
About the Author
