Vertex Receives TGA Approval for ALYFTREK® (vanzacaftor/tezacaftor/deutivacaftor), a once-daily next-in-class CFTR Modulator for the Treatment of Cystic Fibrosis

ALYFTREK^® is now registered by the TGA for Australians with cystic fibrosis aged 6 years and older with at least one responsive CFTR mutation–

Approximately 3,200 Australians may now be eligible for this next-in-class treatment for cystic

fibrosis¹ –

SYDNEY, 20 November 2025 – Vertex Pharmaceuticals today announced that the Therapeutic Goods Administration (TGA) has approved the use of ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor) for the treatment of people aged 6 years and older who meet the diagnostic criteria for cystic fibrosis (CF) and who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical or in vitro evidence².

ALYFTREK is the latest treatment option for CF and 5th CFTR modulator to be approved in Australia; a once daily, triple combination therapy, targeting the underlying cause of the disease by improving CFTR function at and below the cell surface³.

“For more than 20 years, Vertex has worked alongside the CF community to develop therapies that target the cause of this disease,” said Dr. Kasia Siwek, Medical Director, Vertex Pharmaceuticals Australia and New Zealand. “With this TGA registration, more children and adults living with CF in Australia are one step closer to accessing this next in class treatment option for cystic fibrosis. It is a testament to our commitment to serially innovate and continue to improve the lives of people living with CF.”

The TGA registration of ALYFTREK is based on global clinical trials that assessed its safety and efficacy in people with CF aged 6 years and over, supported by real world evidence and in vitro data. Detailed information on side effects, precautions, and dosing is available in the Consumer Medicine Information (CMI).

Patients and caregivers should speak with their treating healthcare professional to understand if ALYFTREK may be suitable for them.

Media Contacts:

Rachael Bylykbashi

Vertex Australia – Communications Director M: +61 427 872 380

E: [email protected]

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 109,000 people, including 3,800 people in Australia. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients.

Today Vertex CF medicines are treating over 75,000 people with CF across more than 60 countries on six continents. This represents 2/3 of the diagnosed people with CF eligible for CFTR modulator therapy.

Diagnosis of CF is often made by genetic testing and is confirmed by testing sweat chloride (SwCl), which measures CFTR protein dysfunction. The diagnostic threshold for CF is SwCl ≥60 mmol/L,

while levels between 30-59 indicate CF is possible and more testing may be needed to make the diagnosis of CF.

Higher levels of SwCl are associated with more severe disease. People with SwCl levels below 60 mmol/L have better lung function, fewer pulmonary exacerbations, better quality of life, and improved survival than those with higher levels of SwCl. Restoring SwCl levels below 30 mmol/L has long been the ultimate treatment goal for Vertex, as levels below 30 mmol/L are considered normal and are typical of CF carriers who do not have disease.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. Globally, the company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 16 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For.

About ALYFTREK^® (vanzacaftor/tezacaftor/deutivacaftor)

▼ This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

Contraindication: Hypersensitivity to the active substance or to any of the excipients.

Precautions: Please refer to PI for complete list. Patients with severe hepatic impairment (Child-Pugh Class C) should not be treated with ALYFTREK. Treatment of patients with moderate hepatic impairment (Child-Pugh Class B) is not recommended. For patients with moderate hepatic impairment, ALYFTREK should only be used if there is a clear medical need and the benefits are expected to outweigh the risks. Assessments of transaminases (ALT and AST) and total bilirubin are recommended for all patients prior to initiating ALYFTREK, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of liver disease or transaminase elevations, more frequent monitoring should be considered. ALYFTREK should be used with caution in patients with pre-existing advanced liver disease (e.g., cirrhosis, portal hypertension) and only if the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment. Cases of noncongenital lens opacities have been reported in paediatric patients treated with ivacaftor containing regimens. Baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating treatment with ALYFTREK.

Interactions: Please refer to PI for complete list. Vanzacaftor, tezacaftor and deutivacaftor are substrates of CYP3A. Concomitant use of CYP3A inducers may result in reduced exposures and thus reduced ALYFTREK efficacy. Coadministration of ALYFTREK with moderate or strong CYP3A inducers is not recommended. Deutivacaftor may inhibit CYP2C9; therefore, monitoring of the

international normalized ratio (INR) during co‑administration of ALYFTREK with warfarin is recommended. ALYFTREK should be used with caution with glimepiride and glipizide. The dose of ALYFTREK should be reduced when co-administered with moderate CYP3A inhibitors such as fluconazole, or strong CYP3A inhibitors such as itraconazole. When used concomitantly with substrates of Breast Cancer Resistance Protein, caution and appropriate monitoring should be used.

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.