#AAN2022 – Ublituximab Bests Aubagio on Disability Measures
The findings were presented in a series of posters at the 2022 American Academy of Neurology (AAN) Annual Meeting, being held in Seattle April 2–7, and virtually April 24–26.
“We are pleased to present additional analyses from the ULTIMATE I & II trials, which continue to highlight encouraging data for ublituximab as a potential treatment for patients with relapsing forms of multiple sclerosis,” Michael Weiss, chairman and CEO of TG Therapeutics, said in a press release.
Like other therapies in its class — including Roche’s Ocrevus (ocrelizumab) and Novartis’ Kesimpta (ofatumumab), both already approved for MS — ublituximab works to reduce disease-driving inflammation by killing immune cells called B-cells.
The Phase 3 clinical trials ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) tested ublituximab against Sanofi Genzyme’s approved MS treatment Aubagio (teriflunomide) in a total of 1,094 people with relapsing MS. About 98% of participants had relapsing-remitting MS, while the rest had active secondary progressive MS.
At AAN, scientists at TG and other institutions performed a number of post hoc analyses (assessments designed and carried out after the trials were already over) of data from the ULTIMATE trials.
In one poster, “Disability Improvements With Ublituximab in Relapsing Multiple Sclerosis (RMS): Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk (T25FW) Evaluations From the Phase 3 ULTIMATE I and II Studies,” researchers assessed how ublituximab treatment affected a number of disability-related outcomes.
Based on Expanded Disability Status Scaled (EDSS) scores, 65 ublituximab-treated patients experienced a confirmed disability improvement, or a lessening in disability, lasting at least 12 weeks in the ULTIMATE trials. By the end of the 96-week (nearly two-year) trials, 95% of these patients sustained the improvements.
Among participants with EDSS scores of 2 or higher at the study’s start, indicating at least minimal disability, 12.6% of ublituximab-treated patients experienced an improvement of at least one point on the EDSS, and 3% improved by at least two points. The proportion of Aubagio-treated patients with similar improvements was markedly lower (7% and 1.1%, respectively).
Significantly more participants treated with ublituximab than Aubagio experienced an improvement of 20% or more in the 9-Hole Peg Test, a measure of manual dexterity — 11.4% vs. 5.5% for the dominant hand, and 11.4% vs. 5.7% for the nondominant hand.
The proportion of participants who experienced at least 20% improvements in the time it took to walk 25 feet, however, was not significantly different between ublituximab and Aubagio.
In another analysis, researchers looked at an outcome called no evidence of disease activity (NEDA-3), defined as no relapses, no new brain inflammation or new and enlarging lesions on MRI scans, and no confirmed worsening in disability.
That poster was titled, “Ublituximab Treatment Is Associated With a Significant Proportion of Patients Achieving No Evidence of Disease Activity (NEDA): Results From the Ultimate I and Ultimate II Phase 3 Studies of Ublituximab vs Teriflunomide in Relapsing Multiple Sclerosis (RMS).”
Results showed that NEDA-3 rates were significantly higher with ublituximab than Aubagio (44.6% vs. 12.4%) over the 96-week trials. Those on ublituximab who experienced disease activity in that period mostly did so due to the presence of new or enlarging lesions on MRI scans, or relapses.
To determine if ublituximab resulted in NEDA-3 at different points throughout the trial, the researchers examined data from weeks 24 to 96, and also from 48 to 96 weeks.
Looking at weeks 24 to 96 (and comparing against week 24), 82.1% of participants given ublituximab had NEDA-3, compared with 22.5% in the placebo group. Similar differences were obtained for the 48–96 week period (and comparing against week 48) — 88.2% vs. 30.4%.
Of note, these differences were seen among patients regardless of whether they had received prior MS treatments, and in patients with both early and late disease.
“ULTIMATE I and II post hoc pooled analyes demonstrated a consistent NEDA benefit for ublituximab-treated patients across treatment epochs and key patient subpopulations,” the scientists concluded.
The third poster, “Infusion-Related Reactions (IRRs) With Ublituximab in Patients With Relapsing Multiple Sclerosis (RMS): Post Hoc Analyses From the Phase 3 ULTIMATE I and II Studies,” detailed safety outcomes in the ULTIMATE studies.
Ublituximab is administered via an infusion into the bloodstream every six months. Pooled analyses showed that 96.6% of ublituximab infusions were completed without interruption.
After the first infusion, most maintenance doses were given in one hour, give or take a few minutes. Of note, Ocrevus infusions take at least two hours, while Kesimpta is given via monthly injection under the skin.
Just fewer than half (43%) of patients treated with ublituximab in the ULITMATE trials experienced an infusion-related reaction (IRR) when they received their first infusion of the therapy. Of these, most (69.5%) did not have any further IRRs with additional infusions.
The most common IRR was fever, in about one out of 10 patients given ublituximab. One serious IRR (an anaphylactic allergic reaction) was reported, but all IRRs eventually were resolved.
“We believe these data reinforce the potential of ublituximab, if approved, to offer RMS patients a treatment option that can be administered in a one-hour infusion every six months after the first dose,” Weiss said.
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting. Go here to see the latest stories from the conference.