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Vyndamax and Vyndaqel
Sponsor
ARTGs
Device/Product name
Vyndamax and Vyndaqel
Active Ingredient
Tafamidis and tafamidis meglumine
Date of decision
Published
Submission type
New chemical entity
ATC codes
N07XX08
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 Vyndamax and Vyndaqel 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 these applications.
These applications were evaluated as part of the Australia-Canada-Singapore-Switzerland (ACSS) Consortium, with work-sharing between TGA and Health Sciences Authority Singapore. Each regulator made independent decisions regarding approval (market authorisation) of the new medicines.
| Description | Date |
|---|---|
| Positive Designation (Orphan) | 23 January 2019 |
| Submission dossier accepted and first round evaluation commenced | 11 April 2019 |
| First round evaluation completed | 3 September 2019 |
| Sponsor provides responses on questions raised in first round evaluation | 1 November 2019 |
| Second round evaluation completed | 6 December 2019 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 7 January 2020 |
| Sponsor's pre-Advisory Committee response | 21 January 2020 |
| Advisory Committee meeting | (Early ACM advice: 1 to 2 August 2019) 7 February 2020 |
| Registration decision (Outcome) | 13 March 2020 |
| Completion of administrative activities and registration on ARTG | 16 March 2020 |
| Number of working days from submission dossier acceptance to registration decision* | 187 |
*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
Soft capsule
Strength
Vyndamax: 61 mg tafamidisVyndaqel: 20 mg tafamidis meglumine
Other ingredients
Vyndamax
Macrogol 400, Polysorbate 20, Povidone, Butylated hydroxytoluene
Gelatin shell (117781): Gelatin, Glycerol, Iron oxide red, Partially dehydrated liquid sorbitol, Sorbitol, Mannitol
Opacode WB water based monogramming ink NSP-78-18022 White (PI 3883): Ethanol, Isopropyl alcohol, Macrogol 400, Polyvinyl acetate phthalate, Propylene glycol, Titanium dioxide, Strong ammonium solution
Vyndaqel
Macrogol 400, Polysorbate 80, Sorbitan mono-oleate
Gelatin shell (116678): Gelatin, Glycerol, Iron oxide yellow, Partially dehydrated liquid sorbitol, Sorbitol, Mannitol, Titanium dioxide
Opacode Purple S-1-10011-N (PI 3413): Ethanol, Isopropyl alcohol, Macrogol 400, Polyvinyl acetate phthalate, Propylene glycol, Carmine, Brilliant Blue FCF, Strong ammonium solution
Containers
Blister pack
Pack sizes
30
Routes of administration
Oral
Dosage
Treatment should be initiated and remain under the supervision of a physician knowledgeable in the management of patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
Vyndamax
The recommended dose of Vyndamax is 61 mg tafamidis orally once daily (see Section 5.1 Pharmacodynamic properties).
A single 61 mg Vyndamax (tafamidis) capsule is bioequivalent to 80 mg Vyndaqel (tafamidis meglumine) (administered as four 20 mg Vyndaqel capsules) and is not interchangeable on a per mg basis (see Section 5.1 Pharmacodynamic properties and Section 5.2 Pharmacokinetic properties).
No dose ranging studies have been undertaken.
Vyndaqel
The recommended dose of Vyndaqel is 80 mg tafamidis meglumine (administered as four 20 mg capsules) once daily.
A dose of 80 mg Vyndaqel (tafamidis meglumine) (administered as four 20 mg Vyndaqel capsules) is bioequivalent to a single 61 mg Vyndamax (tafamidis) capsule and is not interchangeable on a per mg basis (see Section 5.1 Pharmacodynamic properties and Section 5.2 Pharmacokinetic properties).
No dose ranging studies have been undertaken.
For further information refer to the Product Information.
Pregnancy category
DDrugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.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
Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine) was approved for the following therapeutic use:
Vyndamax/Vyndaqel is indicated for the treatment of adult patients with wildtype or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM).
What is this medicine and how does it work
Tafamidis and tafamidis meglumine are selective stabilisers of transthyretin (TTR). Tafamidis and tafamidis meglumine bind with negative cooperativity to the two thyroxine binding sites on the native tetrameric form of TTR preventing dissociation into monomers, the rate-limiting step in the amyloidogenic process. The inhibition of TTR tetramer dissociation forms the rationale for the use of Vyndamax and Vyndaqel to reduce all-cause mortality and cardiovascular-related hospitalisation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients.No studies have been undertaken to establish a direct relationship between this dissociation and an effect on reduction of amyloid deposition in the heart.
What post-market commitments will the sponsor undertake
- Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine) are to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Vyndamax and Vyndaqel 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 Vyndaqel EU-Risk Management Plan (RMP) (version 9.1, dated 31 July 2019, data lock point 1 August 2018), with Australian specific Annex (version 1.1, dated 17 October 2019), included with submission PM-2019-01399-1-3, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
The Vyndamax EU-RMP (version 9.1, dated 31 July 2019, data lock point 1 August 2018), with Australian specific Annex (version 1.1, dated 17 October 2019), included with submission PM-2019-00391-1-3, 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 (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.