Nearly all patients with relapsing multiple sclerosis treated with ublituximab remained relapsed free after 24 weeks.
Edward Fox, MD, PhD
Nearly all patients with relapsing multiple sclerosis (RMS) treated with the novel glycoengineered anti-CD20 antibody ublituximab remained relapsed free with no T1 Gd-enhancing lesions detected on MRI after 24 weeks of follow-up, according to preliminary results of a phase 2a study presented at the 2017 MS Paris Meeting.
In the early findings, 23 of 24 patients (95.8%) treated with ublituximab had a confirmed response after 24 weeks. In B cell data from the participants, there was a rapid depletion of B cells that peaked at week 4 and was maintained to week 24, with a median B cell depletion rate of 99%. There was a 100% drop in T1 Gd-enhancing lesions.
“The clinical and MRI data presented today is highly encouraging and further confirms the compelling efficacy seen in multiple sclerosis patients treated with ublituximab," lead investigator Edward Fox, MD, PhD, Director of the Multiple Sclerosis Clinic of Central Texas and Clinical Associate Professor at the University of Texas Dell Medical School, said in a statement. "While still early, it appears ublituximab can be a highly competitive anti-CD20 with a shorter infusion time, which is a great benefit to our patients."
In preclinical work, ublituximab was shown to be 100 times more potent at inducing nature killer cell-mediated antibody-dependent cellular cytotoxicity than the established CD20 inhibitor rituximab. The agent, which is also being explored for patients with certain types of cancer, has been studied in over 600 patients.
For the phase 2a study, 24 patients were randomized in a 3:1 ratio to receive ublituximab or placebo across 3 cohorts with various dosing strategies. Ublituximab was given at 150 mg as a 4-hour infusion for the first dose in each cohort followed by 450 mg on day 15 for 3, 1.5, or 1 hours, in cohorts 1, 2, and 3, respectively. For the final week 24 dose, the antibody was given as a 600-mg infusion for 1 hour in cohort 3 or a 450-mg infusion for 1.5 or 1 hours in cohorts 1 and 2, respectively. After 28 days, the study was unblinded and patients in the placebo group could cross over to receive ublituximab.
Enrolled participants were approximately 40 years in age and nearly two-thirds were female. A wide spread of disease duration existed between each cohort ranging from a mean of 0.9 (standard deviation [SD], ±1.2) to 15.5 years (SD, ±20.4). Twenty patients had a mean of 2.55 T1 Gd+ lesions at baseline.
At baseline, 87.5% of patients had experienced at least one relapse in the past year or 2 relapses in the past 2 years. Of those specifically relapsing in the prior year, the mean number of relapses was 1.42. Overall, the mean time from relapse to enrollment in the study was 5.77 months. The mean baseline expanded disability status scale (EDSS) was 2.35 (SD, ±0.60).
At week 24, there was no evidence of disease activity for 62.5% of patients. Overall, 87.5% had no evidence of confirmed disability progression, with the mean EDSS dropping -0.35 points (SD, ±0.89) compared with baseline (P = .15). Overall, 79% of patients showed improvements or a stabling of EDSS. On MRI at 24 weeks, 100% of patients did not show signs of T1 Gd+ lesions and 75% did not have new or enlarging T2 lesions.
There was one confirmed relapse in the study, which was experienced by a patient initially randomized to the placebo group. The relapse occurred after the study was unblinded, 12 days after the first infusion of ublituximab at 150 mg. Treatment with ublituximab was continued and the patient remained relapse-free at the time of follow-up.
The most commonly observed all-grade adverse event (AE) with ublituximab was infusion-related reaction (IRR), which was experienced by 29% of patients. These events were all grade 1 or 2 in severity. Intriguingly, there were no treatment-related IRRs in the third cohort, which had the fastest infusion times and the largest total dose. Overall, 11 patients experienced a grade ≥3 AE, only 1 of which was considered related to ublituximab.
"We look forward to additional data from this phase 2 trial and to participating in the phase 3 ULTIMATE trials and advancing this important treatment option,” said Fox.
The ULTIMATE research program contains 2 phase 3 studies for patients with RMS, and is being conducted under a special protocol assessment with the FDA, which could help speed up approval of the medication if the trials are positive. In the trials, ublituximab will be compared with teriflunomide with a primary endpoint of annualized relapse rate (ARR) following 96 weeks of treatment. The enrollment goal for each trial is 880 patients (NCT03277261, NCT03277248).
Fox E, Lovett-Racke, A, Liu Y, et al. Patient characteristics, safety, and preliminary results of a placebo controlled, phase 2a multicenter study of ublituximab (UTX), a novel glycoengineered anti-CD20 monoclonal antibody (mAb), in patients with relapsing forms of multiple sclerosis. Presented at: 7th Joint ECTRIMS - ACTRIMS Meeting; October 25-28, 2017, Paris, France. Abstract P793.