New interim data from the phase 3b ENHANCE trial (NCT05877963) of patients with multiple sclerosis (MS)demonstrated the tolerability of transitioning from treatment with intravenous (IV) anti-CD20 to ublituximab (Briumvi; TG Therapeutics), a novel monoclonal antibody approved therapy for relapsing forms of MS. These results suggest the successful transition of switching from anti-CD20 therapy to ublituximab for this patient population even with elimination of the starting dose.1,2
Cohort 1 (n = 13), given 450 mg infusion of ublituximab in 2 hours, had a median age of 37 years, 77% of participants were women (n = 10) and the median time since MS diagnosis was 4.4 years. In the currently enrolling cohort 2 given 450 mg infusion of ublituximab in 1 hour, 7 of the dosed participants so far had a median age of 45 years, 71% were women (n = 5) and median time since MS diagnosis was of 3.0 years. For both pooled cohorts, premedications administered included IV methylprednisolone (n = 20, 100%), an antipyretic (paracetamol, n = 13, 65%; ibuprofen, n = 7, 35%) and antihistamines (cetirizine, n = 14, 70%; loratadine, n = 6, 30%; diphenhydramine, n = 1, 5%).
Top Clinical Takeaways
- Ublituximab shows promise in the successful transition of patients with MS from intravenous anti-CD20 therapy, as indicated in interim data from the ENHANCE trial.
- In cohort 1, no infusion-related reactions were reported, while in cohort 2, only mild Grade 1 reactions occurred, demonstrating the overall tolerability of the transition.
- ENHANCE aims to provide more data on the efficacy, tolerability, and immunologic parameters associated with transitioning from anti-CD20 therapy to ublituximab.
Presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, by coauthor Barry A. Singer, MD, director and founder of The MS Center for Innovations in Care, the 48-week, multicenter study aimed to investigate the maintenance of efficacy and tolerability of transition from current anti-CD20 therapy to ublituximab in participants with MS. The design of the study includes 2 patient cohorts who receive a starting dose of 450 mg of ublituximab, instead of the 150 mg starting dosage, with varying infusion time between either 1 hour or 2 hours.
In cohort 1, investigators reported no infusion related reactions in any of the administered infusions given to patients. In cohort 2, only 2 participants with MS had Grade 1 infusion related reactions, which were mild transient reactions. These Grade 1 infusion related reactions included 1 patient who had throat irritation and another patient who experienced headache and flushing. Authors noted that all other infusions from both cohorts were completed in the protocol specified time without any interruption or slowing.
All told, transition between treatments for patients with MS may happen to address suboptimal response, tolerability, or even patient convenience. Authors noted that enrollment for ENHANCE is ongoing and additional data on the efficacy, tolerability and immunologic parameters will be reported in the future. Additionally, investigators noted that further data is needed to confirm the efficacy and safety associated with this transition since prior anti-CD20 was excluded from the phase 3 ULTIMATE studies (NCT03277261; NCT03277248), which assessed ublituximab in patients with MS.
At ACTRIMS Forum 2024, additional data from an analysis of the ULTIMATE trials suggested that pseudoexacerbations are expected to contribute equally to both arms in clinical trials which can influence the primary outcome.3 Conducted by senior author Stephen Krieger, MD, associate professor of neurology at Icahn School of Medicine at Mount Sinai, and colleagues, the analysis compared the proportion of patients with relapses to those with n/eT2 MRI lesion in the ublituximab and teriflunomide (Aubagio; Sanofi) arms from the ULTIMATE trials. Researchers applied a stricter relapse definition, requiring n/eT2 lesions on MRI after the relapse event, during the analysis for both arms.
In this analysis of the ULTIMATE trials, the ratio of ublituximab-treated participants with n/eT2 lesions to those with a relapse was 3.32, similar to teriflunomide-treated participants at 3.04. After rebaselining this ratio for teriflunomide-treated participants, the ratio was stable at 3.13 at week 24 while the ratio flipped to 0.27 for those on ublituximab. Following the application of the redefined relapse criteria using MRI-supported relapses, 75 out of 97 relapses (77.3%) in the ublituximab-treated participants and 38 of the 213 (17.8%) of the relapses in the teriflunomide-treated participants were not confirmed. The ublituximab annualized relapse rate (ARR) reduction increased to 87.6% (R, 0.124 [0.074, 0.209]; P <.0001), with ARR at 0.190 for teriflunomide and 0.024 for ublituximab.
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REFERENCES
1. Foley J, Wray S, Miller T, et al. Evaluating the Maintenance of Efficacy and Tolerability of Transitioning From IV Anti-CD20 Therapy to Ublituximab: ENHANCE Study Interim Data. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. P109.
2. TG Therapeutics Announces Presentation of Data for BRIUMVI® in Multiple Sclerosis at the Americas Committee for Treatment and Research in Multiple Sclerosis Annual Forum. News Release. TG Therapeutics. Published March 1, 2024. Accessed March 6, 2024. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-presentation-data-briumvir-multiple
3. Alvarez E, Bodhinathan K, Xu Y, Miskin H, Lee L, Krieger S. MS Relapse Redefined: Addressing the Radiological/Pseudoexacerbation Paradox With High Efficacy Therapy in the ULTIMATE I and II Trials. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. P110.
