ACTRIMS 2023: Most on Briumvi show no MS activity after 6 months
Over 80% of patients had no disease activity for rest of 2-year ULTIMATE trials
More than half of the people with relapsing forms of multiple sclerosis (MS) who received Briumvi (ublituximab) in the ULTIMATE clinical trials had no signs of disease activity over the first six months of the trial — and over 80% of participants had no disease activity for the rest of the studies, which lasted two years in total.
That’s according to a new analysis presented by Briumvi’s developer, TG Therapeutics, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) annual forum, held last week in San Diego, California.
The poster, “Onset and Maintenance of No Evidence of Disease Activity With Ublituximab: Analyses of the Phase 3 ULTIMATE I and II Studies in Participants With Relapsing Multiple Sclerosis,” was presented by Enrique Alvarez, MD, PhD, professor of neurology at the University of Colorado.
Briumvi is given every six months via hour-long infusion
Briumvi was approved in the U.S. late last year to treat relapsing forms of MS. The therapy is administered every six months via an hour-long infusion into the bloodstream.
The approval was supported by data from two identical Phase 3 clinical trials — ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) — which compared Briumvi against the oral MS therapy Aubagio (teriflunomide).
The trials collectively enrolled more than 1,000 adults with relapsing forms of MS, primarily relapsing-remitting MS. Results from the studies showed Briumvi outperformed Aubagio at reducing relapses and preventing brain lesions. It also led to more patients with confirmed disability improvements, meaning less disability, as well as better life quality.
In the ACTRIMS poster, researchers at TG and other institutions conducted an analysis of data from the ULTIMATE studies to assess disease activity among Briumvi-treated patients over the course of the study.
Results showed that, in the first six months after starting on Briumvi, more than half (53.4%) of patients had no evidence of disease activity (NEDA-3) — meaning they had no relapses, no sustained worsening in disability, and no new lesions on MRI scans.
[Briumvi treatment] resulted in a high proportion of participants achieving and maintaining NEDA [no evidence of disease activity] …. The majority of participants maintained NEDA once achieved.
However, because Briumvi may take about six months to exert an effect on disease activity, the researchers examined the proportion of patients who achieved NEDA-3 after that initial period, from month six to the end of the trials.
Data showed that most of the patients who had achieved NEDA-3 in the first six months — 45.2% out of the initial 53.4% — continued to have no evidence of disease activity over the duration of the two-year studies.
There was also a group of patients (36.9%) who initially experienced some disease activity — mainly relapses — during the first six months, but then achieved NEDA-3 after month six and maintained it until the end of the two-year studies.
As such, a total of 82.1% of participants had no evidence of disease activity from month six to the end of the trials, while they were on stable Briumvi treatment. In contrast, over three-quarters (77.5%) of patients on Aubagio experienced disease activity (mainly new or enlarging lesions) from month six through the end of the studies.
An additional 4.8% of participants experienced disease activity in the second half of the first year of the study (weeks 24-48), but then had no activity in the second year. So, in total, 88.2% of participants on Briumvi had no evidence of disease activity in the second year of the study while on stable treatment.
The researchers concluded that Briumvi treatment “resulted in a high proportion of participants achieving and maintaining NEDA [no evidence of disease activity],” noting that “the majority of participants maintained NEDA once achieved.”
Briumvi is designed to kill B-cells, a type of immune cell, by targeting the protein CD20. This mechanism of action is similar to that of the other approved MS therapies Ocrevus (ocrelizumab) and Kesimpta (ofatumumab).
In a separate analysis at ACTRIMS, researchers used data from the ULTIMATE studies to conduct detailed analyses of how starting on Briumvi affects blood cell counts.
The poster, “Early, Transient Shift In Hematologic Parameters Observed With Ublituximab in the ULTIMATE I and II Phase 3 Studies,” was presented by Peiqing Qian, MD, a neurologist at the Swedish Neuroscience Institute, in Washington.
Majority of patients had normal lymphocyte counts by day 8
In the ULTIMATE trials, blood cell counts were assessed at days two and eight after the first infusion. This has not been done for other anti-CD20 therapies, the researchers noted.
Results showed that two days after Briumvi treatment, over 90% of patients had abnormally low counts of lymphocytes, a class of immune cells that includes B-cells as well as T-cells. In more than a third (39.2%) of cases, lymphocyte counts were low enough to be considered severe.
However, the vast majority (81.1%) of patients with low lymphocyte counts at day two had normal lymphocyte counts by day eight, with no recurrence of low lymphocyte counts at later timepoints following treatment.
Out of 52 patients who had severely low lymphocyte levels documented at any point during the trial, two reported this side effect at any time other than the second day after treatment..
“Unique to the ULTIMATE study designs was assessment of laboratory values at Day 2, which revealed a transient decrease in lymphocytes that normalized in the majority of [Briumvi]-treated participants by Day 8,” the researchers wrote, noting that more work is needed to fully understand the mechanisms behind the shift in blood cell counts.
Because lymphocytes are important for fighting infections, low counts might theoretically increase infection risk. The researchers noted that, of all severe infections that occurred in the study, about 10% occurred in patients who had low lymphocyte levels near the time of infection.
Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2023 Feb. 23–25. Go here to see the latest stories from the conference. Follow along on Facebook, Twitter, and Instagram for live updates using the hashtag #actrims2023.