Trikafta (Triple Combination Therapy: Elexacaftor/Tezacaftor/Ivacaftor) Is Only Effective in CF Patients With f508del Gene Mutation
This leaves 10% of CF patients without causal treatment. These are patients with two minimal function alleles, such as nonsense mutations, insertion and deletion mutations, canonical splicing mutations, and processing mutations other than F508del. Due to their low prevalence, these rare mutations have not been thoroughly characterized. Many mutations, however, cause multiple defects [Veit G, Avramescu RG, Chiang AN].
Translation of these potentiator combinations to the clinic should now be a priority.
De Boeck K., Amaral M.D. Progress in therapies for cystic fibrosis. Lancet Respir. Med. 2016;4:662–674.
Veit G., Avramescu R.G., Chiang A.N., Houck S.A., Cai Z., Peters K.W., Hong J.S., Pollard H.B., Guggino W.B., Balch W.E., et al. From CFTR biology toward combinatorial pharmacotherapy: Expanded classification of cystic fibrosis mutations. Mol. Biol. Cell. 2016;
Heijerman H.G.M., McKone E.F., Downey D.G., Van Braeckel E., Rowe S.M., Tullis E., Mall M.A., Welter J.J., Ramsey B.W., McKee C.M., et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial. Lancet. 2019;394:1940–1948.
Middleton P.G., Mall M.A., Drevinek P., Lands L.C., McKone E.F., Polineni D., Ramsey B.W., Taylor-Cousar J.L., Tullis E., Vermeulen F., et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N. Engl. J. Med. 2019;
HIGHLIGHTS OF PRESCRIBING INFORMATION—KALYDECO® (Ivacaftor) Tablets, for Oral Use. [(accessed on 27 February 2020)];2017
Randell S.H., Fulcher M.L., O’Neal W., Olsen J.C. Primary epithelial cell models for cystic fibrosis research. Methods Mol. Biol. 2011