Alyftrek Approved for Cystic Fibrosis

The US Food and Drug Administration (FDA) approved Vertex’ Alyftrek^® (vanzacaftor/tezacaftor/deutivacaftor) on Dec. 20, 2024. It’s a once-daily triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator for treating cystic fibrosis (CF) in people at least six years of age and who have at least one F508del mutation or another mutation in the CFTR gene that is responsive to Alyftrek. While launch plans have not yet been announced, Alyftrek will be available in two fixed-dose combination tablet strengths: 4mg/20mg/50mg and 10mg/50m/125mg. Its recommended dose depends on the patient’s age and weight, and all tablets should be taken with food that contains fat. The wholesale acquisition cost (WAC) is $28,400 for each 28-day carton. Complete prescribing information is available here.

At a Glance

• Brand Drug: Alyftrek (vanzacaftor/tezacaftor/deutivacaftor)
• Manufacturer: Vertex
• Date Approved: Dec. 20, 2024
• Indication:  To treat CF for patients who are six years of age and older and who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
• Dosage Forms Available: Oral tablets in two fixed-dose combination strengths (vanzacaftor/ tezacaftor/deutivacaftor): 4mg/20mg/50mg and 10mg/50m/125mg
• Launch Date: TBD
• Estimated Annual Cost: $370,000
• FDA Designation(s):  Priority Review, Orphan Drug.
• CF is an inherited disease caused by mutations in both of the patient’s cystic fibrosis transmembrane conductance regulator (CFTR) genes – one from each parent. CFTR genes are responsible for the proteins in ion channels on cell surfaces. Ion channels transport water and salts throughout the body. Absent or defective CFTR proteins suppress, break or damage ion channels, which results in thick mucus that disrupts breathing, leads to frequent infections and interferes with digestion. Eventually CF patients may no longer be able to digest food adequately and they may progress to respiratory failure.
• The Cystic Fibrosis Foundation estimates that about 40,000 Americans currently have CF and that about 1,000 new patients, mostly young children, are diagnosed with it annually. Many more CF patients are surviving into adulthood, with about one-half of CF patients in the US now over the age of 18 years.
• By far, the most common genetic mutation in CF is F508del, which makes proteins disintegrate before they can get to the cell surfaces. About 45% of patients have CF caused by two F508dels. Approximately 45% more patients have CF that results from one F508del and another mutation associated with the condition.
• Vanzacaftor and tezacaftor are CFTR correctors, which help to stabilize CFTR proteins at the correct places for ion channels on cell surfaces. Deutivacaftor potentiates CFTR to help keep the ion channels functional, which increases the flow of water and salts into and out of cells.
• In clinical trials, treatment with the Alyftrek was shown to be non-inferior to treatment with Vertex’s Trikafta^® (elexacaftor/tezacaftor/ivacaftor), which is taken twice daily.
• Alyftrek carries a boxed warning indicating that it can cause liver injury and liver failure.  Monitor liver function tests every month during the first six[ months of treatment, then every three months during the next 12 months, then at least annually thereafter.
• To help absorption of Alyftrek by the body, the tablets should be taken with unheated, fat containing food, such as milk, peanut butter or yogurt.