Tezacaftor

Tezacaftor

Clinical data
Trade names	Symdeko (with ivacaftor)
Other names	VX-661
License data	US DailyMed: Tezacaftor
Routes of administration	By mouth
ATC code	R07AX31 (WHO) (combination with ivacaftor)
Legal status
Legal status	CA: ℞-only US: ℞-only
Identifiers
IUPAC name 1-(2,2-Difluoro-1,3-benzodioxol-5-yl)-N-[1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl]-cyclopropanecarboxamide
CAS Number	1152311-62-0
PubChem CID	46199646
DrugBank	DB11712
ChemSpider	28637762
UNII	8RW88Y506K
KEGG	D11041
CompTox Dashboard (EPA)	DTXSID40673070
Chemical and physical data
Formula	C26H27F3N2O6
Molar mass	520.505 g·mol−1
InChI InChI=1S/C26H27F3N2O6/c1-24(2,13-33)22-8-14-7-18(17(27)10-19(14)31(22)11-16(34)12-32)30-23(35)25(5-6-25)15-3-4-20-21(9-15)37-26(28,29)36-20/h3-4,7-10,16,32-34H,5-6,11-13H2,1-2H3,(H,30,35)/t16-/m1/s1 Key:MJUVRTYWUMPBTR-MRXNPFEDSA-N

Tezacaftor is a drug used for the treatment of cystic fibrosis (CF) in people six years and older, who have a F508del mutation, the most common type of mutation in the CFTR gene. It is sold as a fixed-dose combination with ivacaftor under the brand name Symdeko. It was approved by the U.S. FDA in 2018. The combination of elexacaftor, tezacaftor, and ivacaftor is being sold as Trikafta.

In 2019, the U.S. Food and Drug Administration (FDA) approved a combination of elexacaftor, tezacaftor, and ivacaftor.

Mechanism of action

Tezacaftor acts as a corrector to help the folding and presentation of the CFTR protein to the cell surface, which improves its function for individuals with a F508del mutation.

Clinical trials

The EVOLVE and EXPAND study findings were published in 2017.

EVOLVE trial

The EVOLVE trial analyzed tezacaftor/ivacaftor in patients with cystic fibrosis, specifically with the homozygous for Phe508del mutation. The EVOLVE trial is a phase 3, double-blinded, multicenter, randomized, placebo-controlled, parallel-group trial, that was which evaluated therapy with a combination of tezacaftor and ivacaftor in patients that are 12 and older.

510 patients were randomized and 509 patients were given either 100 mg of tezacaftor once daily and 150 mg of ivacaftor twice daily or a placebo for 24 weeks. The combination of drugs was efficacious in patients who had cystic fibrosis with the Phe508del mutation and the adverse effects in both treatment groups were similar.

History

The U.S. Food and Drug Administration (FDA) granted the application for tezacaftor and ivacaftor combination therapy orphan drug designation and priority review, and granted the approval of Symdeko to Vertex Pharmaceuticals Incorporated.

External links

• "Tezacaftor". Drug Information Portal. U.S. National Library of Medicine.
• "Ivacaftor regimen with Tezacaftor". Drug Information Portal. U.S. National Library of Medicine.