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. 2022 Nov 10;16:3915–3927. doi: 10.2147/DDDT.S236926

Table 1.

Pivotal Trials of DRF in MS

Evolve-MS-1 (NCT02634307) Evolve-MS-2 (NCT03093324)
Trial design Phase III, open-label, single-arm study; non-comparative Phase III, randomized, double-blind, head-to-head, 5-week study; superiority
Inclusion criteria Adults aged 18–65 years with a confirmed diagnosis of
RRMS and who were neurologically stable with no
evidence of relapse in the 30 days before screening		 Adults aged 18–65 years with a confirmed diagnosis of
RRMS and who were neurologically stable with no
evidence of relapse in the 30 days before screening
Intervention(s) De novo patients

  • ● DRF 231 mg BID (Week 1)

  • ● DRF 462 mg BID (Weeks 2–96)

  • ● Rollover patients from EVOLVE-MS-2

  • ● DRF 462 mg BID over 96 weeks

  • ● DRF 231 mg BID (Week 1)

  • ● DRF 462 mg BID (Weeks 2–5)
Comparator N/A

  • ● DMF 120 mg BID (Week 1)

  • ● DMF 240 mg BID (Weeks 2–5)
Endpoints

  • ● Relapse

  • ● Disability (EDSS, T25FW)

  • ● Disease progression (CDW3M)

  • ● Freedom from disease activity (NEDA-3, NEDA-4)

  • ● Subclinical disease activity (MRI)

  • ● Adverse effects of treatment

  • ● Health-related quality of life (EQ-5D, SF-12)

  • ● Adverse effects of treatment

  • ● Health-related quality of life (IGISIS, GGISIS)
Enrolment N=1057 as of September 2020 N=696 as of March 2018, median exposure 59.9 weeks (range: 0.1–98.9)
Results

  • ● Treatment discontinuation: 14.9%

  • ● GI TEAEs were reported in 30.9%

  • ● GI TEAEs led to <1% of patients discontinuing treatment.

  • ● Mild or moderate in severity for the vast majority (96%)

  • ● GI AEs occurred early in treatment, mostly resolved (88.8%), and were of short duration [median 7.5 (range 1–87) days] in most patients.

  • ● Treatment discontinuation due to AEs: DRF, 1.6% versus DMF, 5.6%

  • ● Treatment discontinuation due to GI AEs: DRF, 0.8% versus DMF, 4.8%

  • ● Interference with daily activities (IGISIS): DRF, 9.5% versus DMF, 28.9%

  • ● Work productivity (GGISIS): DRF, 6.1% versus DMF, 11.3%

  • ● Days with ⩾1 h of missed work: DRF, 43 days versus DMF, 88 days.

  • ● Concomitant symptomatic medication use: DRF, 19.3% versus DMF, 30.6%

Abbreviations: IGISIS, Individual Gastrointestinal Symptom and Impact Scale; GGISIS, Global Gastrointestinal Symptom and Impact Scale; DMF dimethyl fumarate; DRF, diroximel fumarate, RRMS, relapsing-remitting MS; MS, multiple sclerosis, BID twice a day, EDSS expanded disability status scale; T25FW timed 25-foot walk; MRI, magnetic resonance imaging; NEDA, no evidence of disease activity; CDW3M, confirmed disability worsening over 3 months; EQ-5D, standardised measure of health-related quality of life developed by the EuroQol Group; SF-12, 12-Item Short Form Survey.