ENHANCE Data Suggest Safety of Higher-Dose Ublituximab and Shorter Infusion Time

New data from the ongoing phase 3 ENHANCE study (NCT05877963) of patients with multiple sclerosis (MS) suggest that a 450-mg dose of ublituximab-xiiy (Briumvi; TG Therapeutics) can be administered in 1 hour as the initial infusion for those individuals who are B-cell depleted without additional safety concerns, and a shorter infusion time of 30 minutes was similarly well tolerated.¹ Currently, the therapy is approved by the FDA in a dose of 150 mg (25 mg/mL) in a single-dose vial.²

Among those evaluated for the higher-dose infusion, the most frequently reported symptoms of Grade 1 IRRs were throat irritation (n = 7) and headache (n = 5), with the single Grade 2 IRR—minor throat itchiness—resolving without modification to the infusion. In total, 16% of those who were B-cell depleted (n = 86) reported an IRR after the day 1 dosing, and 8% of those who were not depleted (n = 40) reported an IRR. Notably, all patients had an antipyretic at each infusion.

The data were presented in a poster by John F. Foley, MD, a neurologist and the founder of the Rocky Mountain Multiple Sclerosis Clinic, and colleagues, at the the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held September 18-20, in Copenhagen, Denmark.¹ The 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. According to Foley et al, “neither duration nor dose impacted the completion rate or incidence of infusion modification.”

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 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.

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In ENHANCE, patients were assessed in 3 cohorts: those who were already B-cell depleted from prior anti-CD20 therapy transition to ublituximab and treated with a full dose of 450 mg over 2 hours (cohort 1; n = 13) or 1 hour (cohort 2; n = 21); and those being treated with another disease-modifying therapy (DMT), but not meeting inclusion criteria for cohorts 1 or 2, who transitioned to ublituximab at the labeled dose of 150 mg over 4 hours. This analysis included patients from cohorts 1 and 2, as patients are still being enrolled in the second and third groups.

Patients in the study transitioned to ublituximab from a number of other therapies, including ocrelizumab, natalizumab (Tysabri; Biogen), dimethyl fumarate (Vumerity; Biogen), glatiramer acetate, ofatumumab (Kesimpta Novartis), fingolimod (Gilenya; Novartis), ozanimod (Zeposia; Bristol Myers Squibb), evobrutinib (Merk), teriflunomide (Aubagio; Sanofi), rituximab, and interferon beta-1a. Among the B-cell depleted patients, the vast majority (94%) transitioned from ocrelizumab, while the remaining 6% transitioned from ofatumumab. All told, of the 34 patients included in the analysis who had transitioned to ublituximab from ocrelizumab (Ocrevus; Genentech), 20 (59%) had reported a wearing-off effect on their prior therapy.

Ultimately, the goal of the study was to determine if the elimination of the initial 150-mg dose would affect safety and efficacy, and if faster, higher-dose infusions of 30 minutes at week 24 were safe and tolerable. The data showed a low incidence of infusion-related reactions (IRRs) among patients in the study, regardless of B-cell depletion status, with only a single incidence of a Grade 2 IRR.

These data build upon those presented earlier this year at the2024 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. Those results suggested the successful transition of switching from anti-CD20 therapy to ublituximab for this patient population, even with elimination of the starting dose.³

Click here for more coverage of ECTRIMS 2024.

REFERENCES
1. 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
2. Briumvi (ublituximab-xiyy) prescribing information. FDA. Revised December 2022. Accessed September 18, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761238s000lbl.pdf
3. 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