MSDA Scores Indicate Differing Disease Activity Trajectories With Ublituximab vs Teriflunomide

Data from a subgroup of patents from the phase 3 ULTIMATE studies showed that treatment with ublituximab (Briumvi; TG Therapeutics) resulted in a consistent decrease in disease activity on the Multiple Sclerosis Disease Activity Test (MSDA) over a 96-week period whereas only a handful of those on teriflunomide (Aubagio; Sanofi) experienced the same. Investigators concluded that these data suggest that the MSDA may serve as a quantitative measurement tool for evaluation of disease activity and therapeutic efficacy.¹

Presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held September 18-20, in Copenhagen, Denmark, 100% of ublituximab-treated patients (n = 21) had low disease activity (DA) scores at week 96 in comparison with 30% of those treated with teriflunomide (n = 20). For teriflunomide, 40% of treated patients had moderate DA and 30% had high DA scores, signifying a contrast in impact on disease activity between the 2 therapies.

Led by senior investigator John F. Foley, MD, a neurologist and founder of the Rocky Mountain Multiple Sclerosis Clinic, the analysis aimed to evaluate differences in the trajectories of the overall DA score, 4 Pathway Scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and 18 proteins in ULTIMATE study participants treated with either therapy over a 96-week period. The MSDA, created by Octave Bio, is a blood test drawn that measures disease activity on a scale of 1-10.0. Patients are able to use that numeric score to measure and track disease activity over time.

In the analysis, serum samples from study participants were collected at baseline, and weeks 24, 48, and 96. At baseline, 24% of patients in the ublituximab group had low DA, 57% had moderate DA, and 19% had high DA scores. In comparison, 15% of those on teriflunomide had low DA, 70% had moderate DA, and 15% had high DA scores coming into the study. While this analysis focused on disease activity, additional participant samples from the studies are being assayed in the MSDA test for outcomes of T1 gadolinium lesions, new or enlarging T2 lesions, and active/stable status.

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There has been increased incorporation of the MSDA to test disease activity in patients with MS over the years. The test, ordered by a prescribing healthcare provider, may be used to measure the likelihood of new MS lesions seen on MRI scans. Patients with a high disease activity score have been shown to be more likely to have new MRI lesions than those with moderate or low scores. These scores may change over time, stressing the importance of repeat testing on an ongoing basis to evaluate how well current therapy is working and support any decisions to adjust a care plan.

At ECTRIMS 2024, new data from the ongoing phase 3 ENHANCE study (NCT05877963) suggested that a higher dose of ublituximab at 450 mg administered in 1 hour as the initial infusion may be safe for patients with MS. Currently, the therapy is approved by the FDA in a dose of 150 mg (25 mg/mL) in a single-dose vial. In the study, day 1 dosing was completed by 97% of the patients in the B-cell depleted group, which received the 450-mg dose, and 95% of the patients in the non-depleted group, which received the 150-mg dose.²

There were 3 infusion times assessed in the study of the 450-mg dose: 60 minutes (n = 13), 45 minutes (n = 13), and 30 minutes (n = 12). Of note, only the 45-minute infusion group reported any infusion slowing or interruption (92% completed without any such interruption), while the 60-minute and 30-minute groups reported 100% completion rates. In total, 82% of patients received a nondrowsy antihistamine for this week 24 infusion. There were no infusion related-reactions (IRRs) reported in the 60-minute group, but 1 and 2 patients reported IRRs in the 45-minute and 30-minute groups, respectively. All of these were Grade 1 (itching, throat irritation, and headache), and all resolved completely.

Ublituximab is one of the rather newer FDA-approved medications for MS, joining the market in December 2022. The therapy, administered in a 1-hour infusion, twice yearly following the starting dose, was approved based on data from the phase 3 ULTIMATE trials, which featured 1094 patients with relapsing MS across 10 countries. Both trials, conducted under a special protocol assessment established with the FDA, showed the superior efficacy and safety of ublituximab in comparison with teriflunomide, another relatively newer therapy that received FDA approval in 2012.

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REFERENCES
1. Qureshi F, McCurdy S, Sheng E, et al. Comparison of Multiple Sclerosis Disease Activity (MSDA) Test results between patients treated with ublituximab and teriflunomide in the phase 3 ULTIMATE I and II studies. Presented at: ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Abstract P1516/1382
2. Foley J, Miller T, Wray S, et al. Efficacy and tolerability of ublituximab after transitioning from a different disease modifying therapy: Updates from the ENHANCE study. Presented at: ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Poster P329
3. TG Therapeutics Announces FDA Approval of BRIUMVI™ (ublituximab-xiiy). News release. TG Therapeutics. December 28, 2022. Accessed September 20, 2024. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-fda-approval-briumvitm-ublituximab