The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion April 25, 2025, recommending the approval of alyftrek, a novel combination therapy for cystic fibrosis (CF) [[2]]. Alyftrek, developed by Vertex Pharmaceuticals [[3]], combines CFTR modulators vanzacaftor, Tezacaftor, and Deutivacaftor into a single treatment. This medication is intended for individuals aged 6 years and older who have at least one mutation responsive to the therapy [[3]].

Next Steps: European Commission and AIFA review

Following the CHMP’s positive opinion, Alyftrek will undergo further review by the European Commission and the Italian Medicines Agency (AIFA). These are standard bureaucratic procedures before a drug can be marketed within the European Union and Italy.

Clinical Trial Results: Comparing Alyftrek to Kaftrio

Clinical studies have demonstrated that Alyftrek exhibits effectiveness and safety profiles comparable to those of Kaftrio, another CFTR modulator. Currently, Alyftrek is indicated for patients aged 6 and older, aligning with the age group studied in clinical trials. Kaftrio,in comparison,is approved for use in patients as young as 2 years old.

Key Differences Between Alyftrek and Kaftrio

• Dosage: Alyftrek is administered orally once daily, taken with a fat-containing meal. This once-daily dosing is attributed to its prolonged metabolism compared to Kaftrio.
• Sweat Test Values: Alyftrek has shown to produce a more notable reduction in sweat chloride test values compared to Kaftrio, suggesting a potentially greater correction of the CFTR protein channel and enhanced activity. However, the clinical significance of this difference remains under inquiry.
• lung Exacerbations: Clinical studies indicated a modest decrease in the percentage of lung exacerbations among patients treated with Alyftrek compared to Kaftrio. However, this difference was not statistically significant and requires further evaluation in broader clinical contexts.

Clinical Decision-Making

If Alyftrek receives final approval from the European Commission and AIFA, the decision to prescribe either Kaftrio or Alyftrek will be based on clinical evaluations made by physicians at regional CF centers.