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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
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.
