ALYFTREK

What it is

Alyftrek is a combination of vanzacaftor, tezacaftor and deutivacaftor in film-coated tablets. Two strengths are available: vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg and vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg. Vanzacaftor and tezacaftor are CFTR correctors that bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR to increase the amount of CFTR protein delivered to the cell surface. Deutivacaftor potentiates the channel open probability of the CFTR protein at the cell surface. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.

Approved indications

— Cystic fibrosis in people aged 6 years and older who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical or in vitro evidence.

Dosing overview

Adults and paediatric patients aged 6 years and older are dosed according to weight: those weighing less than 40 kg receive three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once daily, while those weighing 40 kg or more receive two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once daily. Alyftrek should be taken with fat-containing food. When co-administered with moderate or strong CYP3A inhibitors, the dose of Alyftrek should be reduced. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh Class A).

Key safety warnings

Cases of liver failure leading to transplantation have been reported within the first 6 months of treatment in patients with and without pre-existing advanced liver disease taking a similar drug. Elevated transaminases are common in people with cystic fibrosis and have been observed in some people treated with Alyftrek. Assessments of transaminases (ALT and AST) and total bilirubin are recommended for all people prior to initiating Alyftrek, every 3 months during the first year of treatment, and annually thereafter. If a patient develops clinical signs or symptoms suggestive of liver injury, Alyftrek should be interrupted and serum transaminases and total bilirubin should be promptly measured. Dosing should be interrupted if ALT or AST exceeds 5 times the upper limit of normal, or if ALT or AST exceeds 3 times the upper limit of normal with total bilirubin exceeding 2 times the upper limit of normal. Cases of non-congenital lens opacities without impact on vision have been reported in people with cystic fibrosis aged less than 18 years treated with ivacaftor-containing regimens. As deutivacaftor is a deuterated isotopolog of ivacaftor, baseline and follow-up ophthalmological examinations are recommended in people with cystic fibrosis aged less than 18 years initiating treatment with Alyftrek.

Contraindications

Alyftrek is contraindicated in cases of hypersensitivity to the active substance or to any component of the medication.

PBS listing

Two strengths are registered on the ARTG: vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg (ARTG 452345) and vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg (ARTG 452346), both first listed 18 November 2025. The Pharmaceutical Benefits Scheme Advisory Committee (PBAC) deferred its decision in July 2025 pending the TGA Delegate's Overview, considering Alyftrek as effective and safe as elexacaftor/tezacaftor/ivacaftor. PBS listing status and pricing are not yet finalised.

Regulatory history

Alyftrek received approval on 14 November 2025 for the treatment of cystic fibrosis in people aged 6 years and older who have at least one mutation in the CFTR gene that is responsive based on clinical or in vitro evidence. The medicine was registered on the Australian Register of Therapeutic Goods on 18 November 2025.