Diroximel Fumarate Maintains Efficacy in Elderly Populations of Multiple Sclerosis

Author(s):

Over a 96-week period, more older patients with relapsing multiple sclerosis on diroximel fumarate achieved no evidence of disease activity-3 status vs younger patients.

Simon Faissner, MD

New data from the phase 3 EVOLVE-MS-1 study (NCT02634307) showed that treatment with diroximel fumarate (Vumerity; Biogen) resulted in similar efficacy in both younger and older cohorts of patients with relapsing-remitting multiple sclerosis (RRMS).¹

Using a cohort of 1057 patients with RRMS, 158 (14.9%) were classified as older (mean age, 58.8 years) and 899 (85.1%) as younger (mean, 39.6 years). Presented at the 9th Congress of the European Academy of Neurology, held July 1-4, in Budapest, Hungary, data showed an annualized relapse rate reduction of 89.3% (95% CI, 81.7-93.7) and 80.4% (795% CI, 6.9-83.4) in older and younger patients, respectively, over a 96-week treatment period.

Led by Simon Faissner, MD, neurologist at St. Josef-Hospital at Ruhr University Bochum, EVOLVE-MS-1 was the main study that led to diroximel fumarate’s FDA approval in 2018. Both young and older patients included in the analysis had similar rates of female representation (72.1% vs 72.2%) and number of prior disease-modifying therapies (1.2 vs 1.5). At baseline, older patients had fewer gadolinium-enhancing lesions (12.9 [SD, 14.1] vs 16.5 [SD, 14.9]) than younger patients and higher Expanded Disability Status Scale scores (2.57 [SD, 1.4] vs 3.39 [SD, 1.5]).

Throughout the course of the 96-week treatment period, adverse events occurred at a similar rate between older (88%; n = 139) and younger (88.9%; n = 799) patients. AEs led to discontinuation in 16 (10.1%) of older and 69 (7.7%) of younger patients. Among older individuals, the blood/lymphatic system disorder, specifically lymphopenia, accounted for the most common reason to discontinue, occurring in 5 individuals (3.2%). Nervous system disorders, which occurred in 14 individuals (1.6%) were the most common reason for discontinuation among younger individuals on diroximel fumarate.

Despite having a higher disability at baseline, as indicated by EDSS scores, a greater proportion of older patients achieved no evidence of disease activity-3 status after 96 weeks (65.8% vs 36.9%). At the same time point, mean EDSS score change from baseline was 0.09 (SD, 0.82) and 0.03 (SD, 0.66) in older and younger individuals, respectively. Furthermore, older patients experienced mean decreases of 0.1 (SD, 0.78) in number of gadolinium-enhancing lesions while investigators observed mean decreases of 0.8 (SD, 4.05) in the younger population.

Diroximel fumarate, a next-generation oral fumarate, is designed to lead to rapid conversion to monomethyl fumarate, the same pharmacologically active metabolite as diroximel fumarate. The therapy demonstrated improved gastrointestinal tolerability compared with dimethyl fumarate (Tecfidera; Biogen) in the phase 3, randomized, head-to-head, double-blind, 5-week, EVOLVE-MS-2 trial (NCT03093324) published in 2020.

In comparison with dimethyl fumarate-treated individuals, those on diroximel fumarate demonstrated a statistically significant reduction of 46% in the number of days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score greater than 2 (95% CI, 0.54; 0.39-0.75; P = .00003). In addition, lower rates of gastrointestinal AEs such as diarrhea, nausea, vomiting, and abdominal pain, were observed in the diroximel group (34.8% vs 49.0%).²

In 2021, NeurologyLive® launched a video program series on the optimal management of relapsing MS, featuring panelists Fred Lublin, MD; Ravi Dukkipati, MD; Gavin Giovannoni, MD; and Lauren Gluck, MD. In the episode below, the group discussed fumarates like dimethyl and diroximel as viable oral options for patients with the condition.

REFERENCES
1. Faissner S, Goldstick L, Ford C, et al. Safety and efficacy of diroximel fumarate in older patients with multiple sclerosis from the phase 3 EVOLVE-MS-1 study. Presented at: EAN 2023; July 1-4; Budapest, Hungary. EPO-160.
2. Naismith RT, Wundes A, Ziemssen T, et al. Diroximel fumarate demonstrates an improved gastrointestinal tolerability profile compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: results from the randomized, double-blind, phase 3 EVOLVE-MS-2 study. CNS Drugs. 2020;34(2):185-196. doi:10.1007/s40263-020-00700-0.