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General Information

Vumerity (diroximel fumarate) is a novel oral fumarate with a distinct chemical structure.

Vumerity is specifically indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Vumerity is supplied as a capsule for oral administration.

Obtain the following prior to treatment with Vumerity: • A complete blood cell count (CBC), including lymphocyte count. • Serum aminotransferase, alkaline phosphatase, and total bilirubin levels. (See Side Effects)

Dosing Information The starting dosage for Vumerity is 231 mg twice a day orally. After 7 days, the dosage should be increased to the maintenance dosage of 462 mg (administered as two 231 mg capsules) twice a day orally. Temporary dosage reductions to 231 mg twice a day may be considered for individuals who do not tolerate the maintenance dosage. Within 4 weeks, the recommended dosage of 462 mg twice a day should be resumed. Discontinuation of Vumerity should be considered for patients unable to tolerate return to the maintenance dosage. Administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to Vumerity dosing may reduce the incidence or severity of flushing.

Clinical Results

FDA Approval

The FDA approval of Vumerity was based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway. It included data from pharmacokinetic bridging studies comparing Vumerity and Tecfidera to establish bioequivalence, and relied, in part, on the FDA's findings of safety and efficacy for Tecfidera.

The NDA submission also included interim exposure and safety findings from EVOLVE-MS-1, an ongoing, Phase 3, single-arm, open-label, two-year safety study evaluating Vumerity in patients with relapsing-remitting MS. Interim results from EVOLVE-MS-1 at the time of NDA submission included a low overall rate of Vumerity treatment discontinuation due to adverse events (6.3 percent), and a rate of less than one percent of patients who discontinued Vumerity treatment due to gastrointestinal (GI) adverse events. Additional exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared to baseline. The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16. In addition, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3).

Side Effects

Adverse effects associated with the use of Vumerity may include, but are not limited to, the following:

flushing

abdominal pain

diarrhea

nausea

In addition, Vumerity can cause the following serious adverse events. Please see the drug label for detailed information and recommended precautions, including blood testing:

Vumerity can cause anaphylaxis and angioedema after the first dose or at any time during treatment;

Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with dimethyl fumarate (which has the same active metabolite as Vumerity);

Vumerity may decrease lymphocyte counts. In the MS placebo-controlled trials with dimethyl fumarate (which has the same active metabolite as Vumerity);

Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate (which has the same active metabolite as Vumerity) in the postmarketing setting.

Mechanism of Action

Vumerity (diroximel fumarate) is a novel oral fumarate with a distinct chemical structure. The mechanism by which diroximel fumarate exerts its therapeutic effect in multiple sclerosis is unknown. MMF, the active metabolite of diroximel fumarate, has been shown to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans. The Nrf2 pathway is involved in the cellular response to oxidative stress. MMF has been identified as a nicotinic acid receptor agonist in vitro.