FDA
Once-daily CFTR modulator approved for cystic fibrosis
Brand name: Alyftrek
Generic name: vanzacaftor/tezacaftor/deutivacaftor
Manufacturer: Vertex Pharmaceuticals
Approval date: December 20, 2024
FDA approved Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) for the treatment of cystic fibrosis (CF) in patients ≥6 years of age who have at least one F508del mutation or another responsive mutation in the CFTR gene.
Deutivacaftor is a CFTR potentiator, and vanzacaftor and tezacaftor are CFTR correctors.
Efficacy
The efficacy of Alyftrek was evaluated in two 52-week randomized, double-blind, active-controlled trials (SKYLINE 102 [NCT05033080] and SKYLINE 103 [NCT05076149]) comparing Alyftrek and a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA). The two trials enrolled a total of 971 patients ≥12 years of age with CF who have at least one F508del mutation or other ELX/TEZ/IVA-responsive mutations in the CFTR gene.
In both trials, the primary endpoint evaluated non-inferiority in mean absolute change in ppFEV1 from baseline through week 24 and a key secondary endpoint evaluated the mean absolute change from baseline in sweat chloride through week 24 in the Alyftrek and ELX/TEZ/IVA treatment groups.
In both trials, treatment with ALYFTREK resulted in an LS mean difference of 0.2 percentage points in absolute change in percent predicted (pp) FEV1 from baseline through week 24 compared to ELX/TEZ/IVA.
Alyftrek recipients also experienced significantly reduced sweat chloride levels at week 24 compared with ELX/TEZ/IVA in both trials.
Safety
Most common adverse reactions to Alyftrek (≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1%) were cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT and AST, rash, and sinus congestion.
The prescribing information includes a Boxed Warning regarding drug-induced liver injury and liver failure. LFTs including ALT, AST, Alk phos, and bilirubin at baseline and while on treatment is recommended.
Sources:
Vertex Pharmaceuticals. (2024, December 20). Vertex Announces US FDA Approval of ALYFTREK, a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis. [Press release]. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-alyftrektm-once-daily-next
Vertex Pharmaceuticals: Alyftrek (vanzacaftor/tezacaftor/deutivacaftor). [Package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218730s000lbl.pdf