Longitudinal EVOLVE-MS-1 Study Demonstrates Diroximel Fumarate's Effective Profile in Relapsing MS

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Throughout the 96-week EVOLVE-MS-1 trial, the majority of patients with MS experienced stable outcomes with diroximel fumarate treatment.

Barry Singer, MD, director and founder of The MS Center for Innovations in Care

Barry Singer, MD

In late 2023, investigators published final results from the phase 3, 96-week EVOLVE-MS-1 trial (NCT02634307) assessing diroximel fumarate (DMF; Vumerity; Biogen) in patients with relapsing-remitting multiple sclerosis (RRMS). All told, results showed that the disease-modifying therapy was well tolerated over a 2-year period, with favorable efficacy outcomes that were consistent with a previously reported interim analysis.1

EVOLVE-MS-1, a long-term study, included patients who were newly enrolled in the DRF clinical trial program and patients who were eligible to enter having completed the 5-week, randomized, double-blind, phase 3 EVOLVE-MS-2 (NCT03093324) study of dimethyl fumarate (Tecfidera; Biogen) and DMF. The overall population comprised of 1057 patients, including a subgroup of 109 patients who were newly diagnosed.

Led by Barry Singer, MD, director and founder of The MS Center for Innovations in Care, most of the population (75.7%; 800 of 1057) completed the study, with adverse events (AEs) as the most common reason for discontinuation (8.3%). Treatment-emergent AEs, reported in 88.7% of patients over the 96-week treatment period, were mainly mild (28.9%) or moderate (50.3%) in severity. Four deaths occurred, of which the causes were reported as bacterial pneumonia (n = 1), fall (n = 1), hypertensive heart disease (n = 1), and cardiac arrest (n = 1); none of which were considered related to the study treatment.

Overall, patients on DRF demonstrated an 81.6% reduction in the adjusted annualized relapse rate (ARR) in the study compared with the 12 months prior. In newly diagnosed patients, adjusted ARR on DMF was 0.13 (95% CI, 0.07-0.22) compared with 1.15 (95% CI, 1.03-1.29) in the 12 months before study entry, representing a reduction of 89.0% (95% CI, 80.5-93.8; P <.0001). Furthermore, adjusted ARR on DMF was 0.13 (95% CI, 0.11–0.17) for de novo patients, 0.13 (95% CI, 0.09–0.18) for prior DMF patients, and 0.12 (95% CI, 0.09–0.16) for prior DRF patients.

At week 48 and 96, 87.7% and 82.4% of patients, respectively, were relapse-free. Estimates of patients with No Evidence of Disease Activity-3 were 65.4% at week 48 and 41.1% at week 96. At the conclusion of the 96-week period, gadolinium-enhancing lesion count was reduced by 72.2% in the overall population (P <.0001) and by 75.0% in the newly diagnosed subgroup (P = .0149). In the overall population, the mean number of new/newly enlarging T2 lesions was 2.1 (SD, 0.2) from baseline to week 48 and 1.3 (SD, 0.2) from week 48 to week 96.

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The study also assessed timed 25-foot walk (T25-FW) and patient reported outcomes such as the EQ-5D-5L and the SF-12 physical domain. All told, these assessments remained stable in patients over the 96-week period. Median T25-FW recorded in patients on DMF was 5.65 (Q1, 4.7; Q3, 7.25) seconds at baseline and 5.59 (4.65, 7.05) seconds at week 96.

Additional safety data from the study showed that 13.5% of patients experienced an AE within the “cardiac disorders” category and 7.5% experienced AEs within the “liver injury” category. Serious infections were reported in 10/1057 (0.9%) patients: appendicitis (n = 2), bacterial pneumonia (n = 1), cellulitis (n = 1), chronic gastritis (n = 1), pneumonia (n = 1), pharyngeal abscess (n = 1), pharyngitis (n = 1), sepsis (n = 1), and urinary tract infection (n = 1). Malignancies were considered rare, occurring in just 5 of the 1057-patient cohort.

AEs effecting the gastrointestional system were found in 31.9% of patients while flushing/flushing-related AEs were recorded in 37.3% of patients. Gastrointestinal AEs, which mostly occurred within the first month of treatment (47.3%; 159 of 336), were resolved in 91.7% (309 of 337) of patients. Similarly, most patients (80.5%; 317 of 394) had their flushing/flushing-related AEs resolved. For unresolved gastrointestinal and flushing/flushing-related AEs, patients were followed until deemed stable by investigators at the last follow-up visit.

REFERENCE
1. Singer BA, Arnold DL, Drulovic J, et al. Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: final safety and efficacy results from the phase 3 EVOLVE-MS-1 study. Mult Scler J. 2023;29(14). doi:10.1177/13524585231205708
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