Vumerity reduces relapses, lesions over 2 years: EVOLVE-MS-1 study

Nearly two years of treatment with Vumerity (diroximel fumarate) significantly reduced relapse rates by more than 80% in people with relapsing-remitting multiple sclerosis (RRMS), according to the final published details of the EVOLVE-MS-1 clinical trial.

MRI scans also showed the number of active inflammatory lesions and new or enlarging lesions dropped significantly throughout the study. Measures of disability, as well as patient-reported outcomes, remained stable.

Similar benefits were observed in newly diagnosed RRMS patients, newly enrolled in EVOLVE-MS-1, as well as those who transitioned from the previous Phase 3 EVOLVE-MS-2 trial (NCT03093324).

Details of EVOLVE-MS-1 were published in the Multiple Sclerosis Journal in the study “Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study.”

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Vumerity works to reduce inflammation, protect against neuronal damage

Vumerity, marketed by Biogen, is an approved oral disease-modifying therapy (DMT) for relapsing forms of MS. It works to reduce inflammation and protect against neuronal damage, which is expected to reduce disease activity in MS patients.

Vumerity contains an inactive molecule called diroximel fumarate, which turns into its active form, monomethyl fumarate, once inside the body. This is also the active ingredient in Biogen’s older MS treatment Tecfidera (dimethyl fumarate), but the newer drug causes fewer and milder gastrointestinal side effects.

This was shown in a Phase 3 clinical trial called EVOLVE-MS-2, which compared five weeks of treatment with Vumerity versus Tecfidera in 506 people with RRMS. In the trial, reductions in gastrointestinal symptoms also led to fewer treatment discontinuations in Vumerity-treated patients, as well as better quality of life and fewer days of missed work.

Participants who completed EVOLVE-MS-2, and RRMS patients who had not previously participated in any Vumerity trial, could then join the open-label Phase 3 EVOLVE-MS-1 (NCT02634307) study.

All received 462 mg of the medication twice daily for 96 weeks (nearly two years), which, according to interim data reported in 2022, significantly reduced RRMS activity.

Now, EVOLVE-MS-1 researchers have shared final safety and efficacy analyses from the trial.

The study enrolled 1,057 patients, including 464 who received at least one dose of Vumerity or Tecfidera in EVOLVE-MS-2 and 593 who were new to Vumerity — 109 of whom were newly diagnosed. Overall, about three-quarters of participants were women, their mean age was 42.5 years, and about two-thirds had received prior DMTs.

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Vumerity for two years reduced relapse rates by 81.6%

Across all participants, Vumerity treatment for two years significantly reduced relapse rates by 81.6% — from 0.70 relapses per year in the year before entering the study to 0.13 relapses per year over the study’s duration.

Likewise, treatment reduced the annualized relapse rate by 89% in newly diagnosed patients. Similar findings were observed for newly enrolled patients and those who received Vumerity or Tecfidera in EVOLVE-MS-2.

This resulted in 82.4% of patients being free of relapses throughout the two years of EVOLVE-MS-1.

After two years of treatment, the majority of patients (90.2%) did not experience confirmed disability progression, or an increase in disability levels that was confirmed in another appointment at least three months later.

That proportion was similar when researchers examined only newly diagnosed patients (93%), newly enrolled patients (91.1%), and prior EVOLVE-MS-2 patients (88.7% for those on prior Tecfidera and 89.3% for patients previously on Vumerity).

The researchers also examined the impact of treatment on MRI activity, namely on the number of lesions with active inflammation and on the development of new or enlarging lesions, over the trial’s two years.

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Vumerity resulted in 72.7% decrease in number of active lesions after two years

Both types of lesions were significantly reduced with treatment. Vumerity resulted in a 72.7% decrease in the number of active lesions after two years, and the mean number of new or enlarging lesions dropped from 3.4 in the first year of treatment to 2.1 in the second year.

The proportion of patients with no evidence of disease activity, a composite measure defined as no relapses, no confirmed disability worsening, and no new or enlarging or inflammatory lesions, was 41.1%.

Finally, walking abilities and patient-reported quality of life remained stable over the study period.

During the study, a total of 257 patients (24.3%) discontinued treatment, primarily due to adverse events (AEs). AEs occurred in nearly all patients (88.7%), and were mostly mild or moderate in severity. Serious AEs were reported in 11.6% of patients. There were four deaths, none of which were considered related to Vumerity.

Nearly one-third of participants experienced AEs affecting the gastrointestinal tract, most of which were deemed mild or moderate. Some patients also experienced AEs related to the heart, liver, and kidneys.

White blood cell counts also dropped after one year and then remained stable. More than half of patients (56.7%) remained above the lower white cell count limit for the duration of treatment. Prolonged low white cell counts were reported in 14.1% of patients.

“In the phase 3 EVOLVE-MS-1 study, treatment with [Vumerity] was associated with a favorable safety and tolerability profile, as well as favorable clinical and radiological outcomes over the 96-week treatment duration,” the researchers concluded.

The findings provided “further support that [Vumerity] is a valuable option for the treatment of patients with RRMS,” they added.