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Vumerity
Sponsor
Device/Product name
Vumerity
Active Ingredient
Diroximel fumarate
Date of decision
Published
Submission type
New chemical entity
ATC codes
L04AX09
Decision
Approved
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Vumerity was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
Registration timeline
The following table summarises the key steps and dates for this application.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 31 March 2021 |
| First round evaluation completed | 31 August 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 28 October 2021 |
| Second round evaluation completed | 22 December 2021 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 22 December 2021 |
| Sponsor's pre-Advisory Committee response | 14 January 2022 |
| Advisory Committee meeting | 3 and 4 February 2022 |
| Registration decision (Outcome) | 18 March 2022 |
| Completion of administrative activities and registration on ARTG | 21 March 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 197 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
Black triangle scheme
Yes. This product will remain in the scheme for 5 years, starting on the date the product is first supplied in Australia
Dose forms
Capsule, enteric
Strength
231 mg
Other ingredients
Butan‑1‑ol, carrageenan, colloidal anhydrous silica, crospovidone, ethanol, hypromellose, iron oxide black, isopropyl alcohol, magnesium stearate, methacrylic acid‑methyl acrylate copolymer (1:1), microcrystalline cellulose, potassium chloride, potassium hydroxide, propylene glycol, purified talc, purified water, shellac, strong ammonia solution, titanium dioxide and triethyl citrate
Containers
Bottle
Pack sizes
120
Routes of administration
Oral
Dosage
The starting dose for Vumerity is 231 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 462 mg (administered as two 231 mg capsules) twice a day orally. Temporary dose reductions to 231 mg twice a day may be considered for individuals who do not tolerate the maintenance dose. Within 4 weeks, the recommended dose of 462 mg twice a day should be resumed. Discontinuation of Vumerity should be considered for patients unable to tolerate return to the maintenance dose.
For further information refer to the Product Information.
Pregnancy category
B3Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved
Vumerity (diroximel fumarate) was approved for the following therapeutic use:
Vumerity is indicated in patients with relapsing multiple sclerosis to reduce the frequency of relapses and to delay the progression of disability.
What is this medicine and how does it work
The pathophysiology of multiple sclerosis (MS) is multifaceted and propagated through ongoing inflammatory and neurodegenerative stimuli, mediated at least in part by toxic oxidative stress. Preclinical studies indicate that diroximel fumarate pharmacodynamic responses appear to be mediated, at least in part, through activation of the nuclear factor (erythroid derived 2) like 2 (Nrf2) transcriptional pathway, which is the primary cellular defense system for responding to a variety of potentially toxic stimuli through up regulation of antioxidant response genes. Dimethyl fumarate reduces inflammatory responses in both peripheral and central cells and promotes cytoprotection of central nervous system cells against toxic oxidative damage, demonstrating effects on pathways known to exacerbate MS pathology. Dimethyl fumarate has also been shown to up regulate Nrf2 dependent antioxidant genes in patients, confirming clinical pharmacodynamic activity in humans. Vumerity and dimethyl fumarate undergo rapid hydrolysis prior to systemic circulation by esterases and are converted to the primary active metabolite, mycophenolate mofetil (MMF). However, the mechanism by which Vumerity and dimethyl fumarate exert therapeutic effects in MS is not fully understood.
What post-market commitments will the sponsor undertake
- Vumerity (diroximel fumarate) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Vumerity must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the TGA of supply of the product.
- The Vumerity European Union (EU) risk management plan (RMP) (version 1.0, dated 9 September 2021, data lock point 1 September 2020 (Vumerity); 26 March 2021 (Tecfidera)), with Australian specific annex (version 1.0, dated October 2021), included with Submission PM 2021 00385 1 1, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of the approval letter.
The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency’s guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (revision 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- Sponsor to submit results of the Study A 301 to the TGA, when completed.