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The Australian Prescription Medicine Decision Summary provides a short overview of the TGA's evaluation process leading to the registration of a new prescription medicine on the Australian Register of Therapeutic Goods (ARTG).
More in-depth information about the evaluation will be available in the Australian Public Assessment Report (AusPAR) for a particular prescription medicine, which can be found on the AusPAR search page once published.
Australian prescription medicine decision summary
|Product name|| |
|Active ingredients|| |
|ATC codes|| |
|Date of decision|| |
25 October 2019
|Date of entry onto ARTG|| |
1 November 2019
|ARTG numbers|| |
|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.
Novartis Pharmaceuticals Australia Pty Ltd
|Sponsor address|| |
54 Waterloo Rd, North Ryde NSW 2113
|Dose forms|| |
Film coated tablet
0.25 mg and 2 mg
|Other ingredients|| |
Lactose monohydrate, microcrystalline cellulose, crospovidone, glycerol dibehenate and colloidal anhydrous silica.
Each 0.25 mg tablet contains 62.2 mg lactose monohydrate.
Each 2 mg tablet contains 60.3 mg lactose monohydrate.
Polyvinyl alcohol, titanium dioxide, iron oxide yellow (2 mg only), iron oxide red (0.25 mg and 2 mg), black iron oxide (0.25 mg only), purified talc, lecithin, xanthan gum.
|Pack sizes|| |
0.25 mg: 12 film coated tablets (titration pack) and 120 film coated tablets.
2 mg: 28 film coated tablets.
|Routes of administration|| |
Before initiation of treatment with Mayzent the CYP2C9 genotype of the patient should be determined. Mayzent should not be used in patients with a CYP2C9*3*3 genotype.
Treatment has to be initiated with a titration pack that lasts for 5 days. The dose titration starts with 0.25 mg once daily on day 1 and 2, followed by once daily doses of 0.5 mg on day 3 (two tablets of 0.25 mg), 0.75 mg on day 4 (three tablets of 0.25 mg), and 1.25 mg on day 5 (five tablets of 0.25 mg), to reach the maintenance dose of 2 mg* Mayzent starting on day 6. *The recommended maintenance dose is 1 mg daily for patients with CYP2C9 *2*3 or *1*3 genotype (for further information on maintenance dosing please see the Product Information). During the first 6 days of treatment initiation the recommended daily dose should be taken once daily in the morning with or without food.
For further information refer to the Product Information.
Mayzent (siponimod) was approved for the following therapeutic use:
Mayzent is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS).
Siponimid is a selective immunosuppressant.
Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds selectively on two out of five G-protein-coupled receptors (GPCRs) for S1P, namely S1P1 and S1P5. By acting as a functional antagonist on S1P1 receptors on lymphocytes, siponimod prevents egress from lymph nodes. This reduces the recirculation of T-cells into the central nervous system (CNS) to limit central inflammation. Siponimod spares effector memory T cells in peripheral tissues and blood and does not impair lymphocyte activation.
Siponimod readily crosses the blood brain barrier.
In animal studies direct effects have been demonstrated for siponimod on neural cells, via S1P1 on astrocytes and S1P5 on oligodendrocytes. In a mouse model of experimental autoimmune encephalomyelitis a direct neuroprotective effect, independent from effects on lymphocytes, was also demonstrated for siponimod applied centrally (via intracerebroventricular infusions).
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 Mayzent was considered favourable for the therapeutic use approved.
The following table summarises the key steps and dates for this application.
|Submission dossier accepted and first round evaluation commenced||30 November 2018|
|First round evaluation completed||5 June 2019|
|Sponsor provides responses on questions raised in first round evaluation||27 June 2019|
|Second round evaluation completed||22 August 2019|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||3 September 2019|
|Sponsor's pre-Advisory Committee response||16 September 2019|
|Advisory Committee meeting||4 October 2019|
|Registration decision (Outcome)||25 October 2019|
|Completion of administrative activities and registration on ARTG||1 November 2019|
|Number of working days from submission dossier acceptance to registration decision*||209|
*Statutory timeframe for standard applications is 255 working days
- Mayzent (Siponimod) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Mayzent 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 Mayzent (Siponimod) EU-Risk Management Plan (RMP) (version 1.1; date 18 March 2019; data lock point 31 December 2017), with Australian Specific Annex (version 2.0; date 17 June 2019), included with submission number PM-2018-04434-1-1, to be revised to the satisfaction of 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).
Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of this approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of this approval letter. The annual submission may be made up of two PSURs each covering six months. If the sponsor wishes, the six monthly reports may be submitted separately as they become available.
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 (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the data lock point for that report.