dm+d

Unassigned

New Medicines

VumerityRelapsing remitting multiple sclerosis (MS)

Information

Vumerity
New molecular entity
Biogen
Biogen

Development and Regulatory status

Launched
Approved (Licensed)
Launched
February 2022
Feb 22Vumerity 231mg gastro-resistant capsules available in the UK. Price for 120=£1471.07 [19].
Nov 21Approved in UK [16]
Nov 21Approved in EU [15].
Sep 21Recommended for EU conditional approval by CHMP – “for the treatment of adult patients with relapsing remitting multiple sclerosis.” Vumerity will be available as 231mg gastro-resistant capsules [14].
Jan 21Filed in EU via centralised procedure [12].
Nov 20Launched in US [13].
Oct 19FDA has approved Vumerity (diroximel fumarate) for relapsing forms of multiple sclerosis [10].
Dec 18Filed in the US [7]
Dec 17Company intends to file in US by 2018 [4]
Dec 17Alkermes signs a global license and collaboration agreement with Biogen for development and commercialisation [4]
Mar 17Alkermes is to initiate a PIII study vs. dimethyl fumarate to evaluate comparative tolerability. This study is part of the company EVOLVE-MS programme intended to support a New Drug Application (NDA) to the US FDA in 2018 [3].
Nov 15Based on a meeting with the US FDA, Alkermes plans to file a New Drug Application (NDA) using pharmacokinetic bridging data from studies comparing ALKS 8700 and Tecfidera, as well as a two-year PIII safety study in approximately 600 patients in 2018. Alkermes is not required to conduct a separate PIII efficacy study in patients with MS. In addition, Alkermes intends to initiate a randomized, head-to-head study comparing the GI tolerability of ALKS 8700 and Tecfidera in approximately 420 patients with MS in mid-2016 [1].

Category

Prodrug of monomethyl fumarate (MMF) in a controlled-release formulation that rapidly and efficiently convert to MMF in the body.
NICE estimate the incidence and prevalence of MS equivalent to 3.5-6.6 per 100,000 people and 100-120 per 100,000, respectively, in England and Wales. About 80-90% of those newly diagnosed have RRMS.
Relapsing remitting multiple sclerosis (MS)
Oral

Further information

Yes

Trial or other data

Feb 22Results from PIII EVOLVE-MS-1 trial (n=1057) show that adjusted annualised relapse rate was 0.13 (95% CI 0.11–0.15) overall, representing an 81% reduction from baseline. Proportion of pts who were relapse-free at week 96 was 82.4%; with 38.4% having no evidence of disease activity by week 96. Significant reductions (63%) in mean no of gadolinium-enhancing lesions were observed from baseline. The percentage of pts who were Gd+ lesion-free at week 96 was 91.2% vs. 69.0% at baseline. Mean number of new/newly enlarging T2 lesions remained stable or declined slightly from Year 1 to Year 2. Overall, 23.3% discontinued treatment; 8% due to adverse events and <1% due to GI AEs. AEs occurred in 88.2% which were mostly mild/moderate in severity. GI AEs occurred in 31.6%. [17,18]
Nov 20Biogen releases new date from VUMERITY PIII clinical program. Findings from the five-week EVOLVE-MS-2 study reinforce clinically meaningful improvements in patient-assessed GI tolerability associated with VUMERITY treatment (n=253) combared to TECFIDERA (n=251), and support its impact on quality of life for people with relapsing MS. Patients taking VUMERITY reported a lower likelihood of experiencing GI symptoms that interfered with daily activities or were associated with missed work, as well as less concomitant medication use to treat GP symptoms. An exploratory analysis from the ongoing EVOLVE-MS-1 study assessed effects of VUMERITY on brain volume change and other clinical measures in people with relapsing MS (n=365) treated for up to two years. Separate studies have shown brain volume loss may be associated with cognitive impairment, physical disability and reduced quality of life in people with MS. Data from EVOLVE-MS-1 show the annual rate of brain volume change in study participants treated with VUMERITY for two years was similar to the rate observed in healthy individuals and approximately 90% of people treated with VUMERITY remained free from confirmed disability progression and ~84% were relapse-free at two years [11].
Jul 19Alkermes announce positive results from PIII EVOLVE-MS-2 trial; diroximel fumarate had fewer reports of significant GI symptoms from patients vs dimethyl fumarate (p=0.0003), and a lower rate of discontinuations due to GI ADRs (0.8% vs 4.8% [9].
Jun 19Pivotal trial EVOLVE-MS-1 (NCT02634307) still recruiting by invitation. Primary and study completion due December 2020 [8].
Nov 18Two PIII trials are underway. EVOLVE-MS-1 (NCT02634307) and EVOLVE-MS-2 (NCT03093324) [6].
Mar 17PIII long term safety and tolerability trial NCT02634307 started - the open label single group study (estimated n=800) has a primary outcome of incidence of adverse effects up to 96 weeks, and estimated primary completion date is Dec 2020 [4].
Nov 15 Alkermes completed a randomised, double-blind PI comparative pharmacokinetic study evaluating plasma MMF levels achieved by administration of single doses of ALKS 8700 and Tecfidera. Initial data from this study showed that ALKS 8700 met the pharmacokinetic criteria for bioequivalence to Tecfidera. Most common AEs were flushing, dizziness and constipation for ALKS 8700, and flushing, nausea and diarrhoea for Tecfidera [1].
Nov 15Alkermes initiated a PI dose-escalation trial to assess safety, tolerability and pharmacokinetics of oral ALKS 8700 in 104 healthy volunteers in the US (ALK8700-001; NCT02201849) [2].

Evidence based evaluations

SMC