In a new analysis of the EVOLVE-MS study, patients treated with diroximel fumarate (Vumerity) appeared to have no detrimental changes in brain volume, researchers reported at the 2021 virtual meeting of the American Academy of Neurology.
“Interim findings from the ongoing EVOLVE-MS-1 study demonstrate that yearly percent brain volume change in diroximel fumarate-treated patients approached the rate observed in healthy adults and was consistent with previous studies of dimethyl fumarate,” reported Jiwan Oh, MD, PhD, medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital of the University of Toronto.
In addition, Oh and colleagues said that after the first 48 weeks, the estimated proportion of patients who were free of confirmed disability progression while on diroximel fumarate was 94.3%; at 96 weeks, 90.7% of the patients on diroximel fumarate were free of confirmed disability progression.
In a post hoc analysis of the EVOLVE-MS-1 study, the researchers noted that diroximel fumarate is an oral fumarate that has been approved for relapsing/remitting forms of multiple sclerosis. Oh explained that diroximel fumarate has the same pharmacologically active metabolite as dimethyl fumarate and is expected to have a similar efficacy/safety profile. Annual rates of brain volume loss with dimethyl fumarate over six years ranged from −0.19% to −0.37%, similar to healthy adults (−0.1% to −0.3%), she reported in her poster presentation.
The researchers included 365 patients in the analysis as of July 2, 2019. The median exposure to treatment was 96 weeks, although it ranged from 75 weeks to 100 weeks at the time of the analysis, the research team reported. At week 48, patients treated with diroximel fumarate averaged −0.36% brain volume change; from week 48 to week 96, the percent brain volume change was −0.36%.
The proportion of patients with no evidence of disease activity at week 48 among patients on diroximel fumarate was 44.7%—that’s 163 of 365 patients; at 96 weeks, 25.2% of patients on diroximel fumarate—91 of 361 patients—had achieved a “no evidence of disease activity” assessment, Oh reported.
In the open-label study, the researchers included patients who had undergone baseline normalized brain volume measurements. That measurement was used to calculate differences in brain volume change when those tests were performed at 48 weeks and at 96 weeks.
Oh reported that for the study, confirmed disability progression was measured using the Expanded Disability Status Scale, with changes sustained for 12 weeks. No evidence of disease activity was defined as no relapses, no 12-week confirmed disability progression, and no new or enlarging T2 or new gadolinium-enhancing lesions.
In the overall study that included 447 patients, treatment with diroximel fumarate reduced the annualized relapse rate by 84.6% compared with the previous 12-month history of the patients. That annualized rate of relapses was 0.81%, but with treatment with diroximel fumarate, the annualized relapse rate decreased 0.12%, researchers reported.
At 96 weeks of treatment in the open-label study, 82.8% of the patients were free of relapse, the researchers reported.
Asaff Harel, MD, assistant professor of neurology, at Lenox Hill Hospital, Northwell Health, New York City, told BreakingMED, “These are not groundbreaking results, but they do give more information about the treatments that we have available. This agent diroximel fumarate is thought to be better tolerated than dimethyl fumarate.
“Although this is not a head-to-head study, it does tell us… what we expect—comparable efficacy with other treatments that are available,” Harel said. “In this analysis, the brain volume change seen in patients with multiple sclerosis who are treated with diroximel fumarate… is about what we would expect to see in the normal population.”
However, he suggested there are limitations to the study. “This was a relatively short study of just 96 weeks,” Harel said, “but the vast majority of patients didn’t have worsening of disability—after two years, more than 90% of the patients had no reduction in disability scores.
“With multiple sclerosis, especially among people who do not have very aggressive, bad disease, we are trying to look 40 or 50 years down the road, so while these results at 96 weeks have good results, longer term follow-up is necessary,” Harel said.
A post hoc analysis of the open-label EVOLVE-MS-1 study found no changes in brain volume with diroximel fumarate therapy.
These data were presented as an abstract at a medical meeting and should be considered with caution until such time the results are published in a peer-reviewed journal.
Edward Susman, Contributing Writer, BreakingMED™
The study was supported by Biogen.
Harel had no disclosures.
Oh disclosed relationships with Biogen, Celgene EMD Serono, Novartis, Roche and Sanofi-Gemzyme, Frequency Therapeutics, MedDay, Merck, Sanofi, and Immunotec.
Cat ID: 36
Topic ID: 82,36,728,791,730,36,192,925,167