New data from two phase 3 studies showed that the new anti-CD20 monoclonal antibody drug ubituximab is associated with significant improvements in multiple sclerosis functional composite (MSFC) scores in patients with relapsing multiple sclerosis (MS), one Measure of disability versus teriflunomide (Aubagio).
The results were presented by Lawrence Steinman, MD, of Stanford University in California, at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held virtually this week.
The previously reported main results of the Phase 3 ULTIMATE I and II studies showed a significant reduction in the annualized recurrence rate (ARR) over 96 weeks (22 months) with ubituximab compared to teriflunomide and a significant reduction in MRI lesions. and improvements in the number of patients with no evidence of disease activity (NEDA).
The data from these two studies will be used to support a recent filing with the US Food and Drug Administration for ubituximab for the treatment of patients with relapsing-remitting MS.
Although ubituximab was associated with an increased proportion of patients with confirmed disability improvement at 12 and 24 weeks compared to teriflunomide, there was no significant difference between the two groups in confirmed disability progression.
Another ULTIMATE investigator, neurologist Bruce Cree, MD, PhD from the University of California San Francisco, stated that the measures of confirmed disability improvement and progression used in clinical trials of MS were responsive to changes in the Expanded Disability Status Scale ( EDSS). However, he pointed out that using this scale is challenging because it usually changes little over the course of a study. He adds that the scale can also be variable.
“Since confirmed disability worsening was not met as a secondary endpoint, one of the criticisms in these studies might be that there was no effect from ubituximab. But disability worsening was rare in both treatment arms, so it would be very difficult.” , if not impossible, to show a difference without including many more patients, ”he said.
Cree noted that the Multiple Sclerosis Functional Composite (MSFC) score is an alternative, more sensitive measure of disability that includes three different tests: the 9-hole peg test, which assesses the mobility of the upper arms; the 25-foot timed walk test, which measures walking ability; and the stimulated auditory serial addition test (PASAT), a measure of attention and processing.
He reported results showing that ubituximab significantly improved the MFSC score for ULTIMATE I by 76% and by 89% for ULTIMATE II compared to teriflunomide. In ULTIMATE 1, the MSFC score improved 0.266 points in the teriflunomide group and 0.469 points in the ubituximab group (P = 0.048) during the 96-week study. In ULTIMATE II, the MSFC score improved by 0.275 points in the teriflunomide group and by 0.521 points in the ubituximab group (P = 0.017).
These changes were driven by improvements in the 9-hole peg test and the 25-foot timed walk test, with no difference seen on the PASAT test.
When asked how ubituximab compares to other anti-CD20 antibodies already in use, such as ocrelizumab (Ocrevus), Cree found that ubituximab is associated with fewer infusion reactions so it can be infused faster. It is given over just 1 hour compared to several hours taken for the ocrelizumab infusion.
“In the ULTIMATE studies, the only reaction with ubituximab during the infusion was a slight increase in temperature, which can be minimized by pretreatment with paracetamol. The allergic reactions such as itching and scratching that were observed with ocrelizumab infusions were far less common with ubituximab. “
Cree attributes this to the glycol engineering of the ubituximab antibody, which he says “allows the cytokines released by the B cells to be metabolized in the phagocytes rather than released into the bloodstream.”
The ULTIMATE studies were funded by TG Therapeutics.
European Committee for the Treatment and Research of Multiple Sclerosis (ECTRIMS). Presented on October 14, 2021.
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