The US Food and Drug Administration approved expanded indications for vanzacaftor/tezacaftor/ivacaftor (ALYFTREK) and elexacaftor/tezacaftor/ivacaftor and ivacaftor (TRIKAFTA), increasing eligibility for cystic fibrosis transmembrane conductance regulator modulator therapy to approximately 95% of patients with cystic fibrosis in the US, according to a press release from Vertex Pharmaceuticals.

The updated indications apply to patients aged 6 years and older for vanzacaftor/tezacaftor/ivacaftor and those aged 2 years and older for elexacaftor/tezacaftor/ivacaftor and ivacaftor who have variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that demonstrate responsiveness in clinical or in vitro data or that result in production of the CFTR protein. Following this expansion, approximately 800 additional patients in the US became eligible for a therapy that addresses the underlying cause of the disease.

The label expansion was supported by clinical and in vitro data evaluating 564 variants for vanzacaftor/tezacaftor/ivacaftor and 521 variants for elexacaftor/tezacaftor/ivacaftor and ivacaftor. The updated indications include variants that are responsive or that result in production of the CFTR protein.

Cystic fibrosis (CF) is a progressive, multi-organ genetic disease affecting the lungs, pancreas, gastrointestinal tract, and other systems. It is caused by defective or absent CFTR protein due to mutations in the gene. This leads to the buildup of thick, sticky mucus, chronic lung infections, and progressive lung damage. The median age of death is in the 30s, although survival has improved with treatment.

Elevated transaminases were observed in patients receiving vanzacaftor/tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor and ivacaftor have been associated with serious and potentially fatal drug-induced liver injury, including cases of liver failure leading to transplantation and death. Liver function tests are recommended prior to initiation, monthly during the first 6 months of treatment, every 3 months for the following 12 months, and at least annually thereafter. Use is not recommended in patients with moderate hepatic impairment and should not be used in those with severe hepatic impairment unless there is a clear medical need and benefit outweighs risk.

Hypersensitivity reactions, neuropsychiatric events, intracranial hypertension, and drug interactions with CYP3A inducers and CYP3A inhibitors have been reported. Common adverse reactions included cough, upper respiratory tract infection, headache, gastrointestinal symptoms, rash, and elevations in liver enzymes.

Vertex reported that its CF therapies are currently used by more than 75,000 patients globally.

Source: Vertex Pharmaceuticals