FDA New Drug and Biologic Approvals, 2018 Midyear Review

Cystic Fibrosis: Symdeko (tezacaftor/ivacaftor)

Indication: Indicated for cystic fibrosis (CF) in patients aged 12 years or older who are homozygous for the F508del mutation or who have at least 1 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

Mechanisms:

Tezacaftor: CFTR corrector; increases amount of mature CFTR protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein.

Ivacaftor: CFTR potentiator; enhances function of the CFTR protein once it reaches the cell surface.

Dosage:

• Copackaged as a fixed dose combination tablet of tezacaftor 100 mg and ivacaftor 150 mg PLUS a separate ivacaftor 150mg tablet.

• Morning dose: One tezacaftor/ivacaftor 100-mg/150-mg fixed-dose tablet PO.

• Evening dose: One ivacaftor 150-mg tablet PO.

• Administer morning and evening doses ~12 hr apart.

Approval was based on the EVOLVE and EXPAND phase 3 trials. Results showed treatment with tezacaftor/ivacaftor and ivacaftor measured improvements across multiple disease measures, including lung function and pulmonary exacerbations compared with ivacaftor monotherapy.

References:

• Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. https://www.nejm.org/doi/10.1056/NEJMoa1709846?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

• Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. https://www.nejm.org/doi/10.1056/NEJMoa1709847?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

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Cite this: Mary L Windle. FDA New Drug and Biologic Approvals, 2018 Midyear Review - Medscape - Aug 01, 2018.