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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
|Submission type|| |
New chemical entity, New fixed dose combination
|Product name|| |
|Active ingredients|| |
Elexacaftor/tezacaftor/ivacaftor, and ivacaftor
|ATC codes|| |
R07AX32 (elexacaftor/tezacaftor/ivacaftor) and R07AX02 (ivacaftor)
|Date of decision|| |
17 March 2021
|Date of entry onto ARTG|| |
24 March 2021
|Original publication date|| |
8 April 2021
|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
Vertex Pharmaceuticals (Australia) Pty Ltd
|Sponsor address|| |
Suite 3, Level 3, 601 Pacific Highway, St Leonards, NSW 2065, Australia
|Dose forms|| |
Tablet, film coated
100 mg elexacaftor/50 mg tezacaftor/75 mg ivacaftor and 150 mg ivacaftor
|Other ingredients|| |
Elexacaftor/tezacaftor/ivacaftor tablets: hypromellose, hypromellose acetate succinate, sodium lauryl sulfate, croscarmellose sodium, microcrystalline cellulose, magnesium stearate, and Opadry complete film coating system 20A130036 orange
Ivacaftor tablets: silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, carnauba wax. Opadry II complete film coating system 85F90614 blue, and Opacode monogramming ink S-1-17823 black
Composite blister pack
|Pack sizes|| |
84 (56 elexacaftor/tezacaftor/ivacaftor tablets and 28 ivacaftor tablets)
|Routes of administration|| |
Adults, adolescents, and children aged 12 years and older
The recommended dose is two tablets (each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) taken in the morning and one tablet (containing ivacaftor 150 mg) taken in the evening, approximately 12 hours apart.
For further information refer to the Product Information.
|Pregnancy category|| |
Drugs 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.
Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) was approved for the following therapeutic use:
Trikafta is indicated for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Elexacaftor and tezacaftor are cystic fibrosis transmembrane conductance regulator (CFTR) correctors that bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface.
The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport. Clinical outcomes were consistent with in vitro results and indicate that a single F508del mutation is sufficient to result in a significant clinical response (see Clinical Efficacy section of the Product Information).
The following table summarises the key steps and dates for this application.
|Designation (Orphan)||11 December 2019|
|Submission dossier accepted and first round evaluation commenced||31 March 2020|
|First round evaluation completed||31 August 2020|
|Sponsor provides responses on questions raised in first round evaluation||30 September 2020|
|Second round evaluation completed||12 November 2020|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||23 December 2020|
|Sponsor's pre-Advisory Committee response||18 January 2021|
|Advisory Committee meeting||4 and 5 February 2021|
|Registration decision (Outcome)||17 March 2021|
|Completion of administrative activities and registration on ARTG||24 March 2021|
|Number of working days from submission dossier acceptance to registration decision*||218|
*Statutory timeframe for standard applications is 255 working days
- Trikafta (elexacaftor/tezacaftor/ivacaftor) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Trikafta must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the Therapeutic Goods Administration (TGA) of supply of the product.
- The Trikafta European Union (EU)-risk management plan (RMP) (version 1.1, dated 21 August 2020; data lock point dated 20 July 2020), with Australian specific Annex (version 2.0, dated 18 September 2020), included with submission PM-2020-00642-1, 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 (Rev 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.