AAN 2025: Real-world study of Briumvi for relapsing MS enrolling
Phase 4 ENABLE trial to enroll about 500 adult patients across 100 US sites
A Phase 4 observational study called ENABLE is enrolling adults with relapsing forms of multiple sclerosis (MS) across the U.S. to better understand the safety, tolerability, and efficacy of Briumvi (ublituximab-xiiy) in the real world.
At least 500 patients are expected to enter ENABLE (NCT06433752) at some 100 clinical sites, representing different regions and racial or ethnic backgrounds. The study has so far enrolled 177 patients, mostly white women, and participants will be followed over the course of about two years.
Details from the trial and enrolled participants were presented in a poster, titled “ENABLE: The First Phase 4 Observational Study for Patients with Relapsing MS Treated with Ublituximab in Real World Clinical Setting,” at the American Academy of Neurology (AAN) 2025 annual meeting, held April 5-9 in San Diego and online. The study is supported by TG Therapeutics, which developed and markets Briumvi.
In MS, immune cells such as B-cells drive an inflammatory attack that damages nerve cells in the brain and spinal cord, leading to symptoms.
Given as an infusion into the bloodstream every six months after two initial shorter-spaced doses, Briumvi works to deplete B-cells, preventing them from taking part in the inflammatory attack that drives MS.
Briumvi approved in US for adults with relapsing forms of MS
Briumvi is approved in the U.S. to reduce relapses and brain lesions, and slow disability progression in adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. The approval was supported by data from the ULTIMATE clinical trials (NCT03277261 and NCT03277248), which ran for 96 weeks, or nearly two years.
Now, TG is seeking to better understand the real-world experience of people treated with Briumvi in a routine clinical setting. For that, the company is sponsoring an observational study which will follow patients who are receiving Briumvi for the first time over a period of 96 weeks.
“We plan to further evaluate the efficacy and tolerability of Briumvi in the real world setting through the ENABLE Phase 4 96-week observational study,” Michael S. Weiss, CEO and chairman of TG Therapeutics, said in a company press release.
Of the first 177 patients enrolled so far, 72.9% are women, and 70.1% are white. The proportion of Black or African-American patients is much higher than in the ULTIMATE clinical studies (19.8% vs. 1.5%), consistent with the objective of broadening the racial or ethnic backgrounds of the study population.
On average, the enrolled patients are older than those who took part in the ULTIMATE studies (42.8 vs. 35.4 years), and they have a “slightly longer” disease duration (8.8 vs. 7.4 years). Most patients had either one relapse (28.8%) or no relapse (44.1%) in the two previous years, with an average of 0.6 relapses in that time window.
Study to assess changes in annualized relapse rate after 96 weeks
The study’s main goal is to watch for changes in the annualized relapse rate, or the number of relapses adjusted to a one-year time window, after 96 weeks. Secondary goals include the proportion of patients experiencing side effects, and the severity and type of infusion-related reactions with each infusion.
A number of patient-reported outcome measures will also be assessed, along with changes in disability levels, walking function, cognition, dexterity, and lesions, among other outcomes.
“ENABLE is the first Phase 4 observational study that will provide valuable real-world clinical evidence on the effectiveness, safety, and tolerability of [Briumvi] from MS centers across the US,” researchers wrote in the presentation.
At the AAN meeting, two other presentations included data from Briumvi studies. In one presentation, researchers surveyed doctors from 21 clinical centers in the U.S. to assess how people with relapsing forms of MS tolerated Briumvi in the real-world setting. Data from 401 adults showed the infusions were well tolerated, being completed in the specified time.
Infusion-related reactions after the first infusion were about half as common in the clinics as in the ULTIMATE studies, possibly because most patients were given the anti-fever medication acetaminophen before the infusion, which was not used in the trials.
In another presentation, researchers shared new data from the open-label extension study (NCT04130997) that followed the ULTIMATE trials. Patients received Briumvi in this extension for up to five years, and the number of serious infections remained constant over time and was not linked to reductions in levels of circulating antibodies, which are produced by B-cells.
“We were pleased to share three presentations yesterday which we believe demonstrate our continued commitment to improving the patient experience and understanding the long term and real-world profile of Briumvi,” Weiss said.
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