Symkevi (EU), Symdeko (US)Cystic fibrosis, homozygous for F508del mutation in the CFTR gene OR heterozygous for F508del and a residual function (RF) mutation (F/RF), in patients aged 6 to 11 years
Symkevi (EU), Symdeko (US)
New formulation and licence extension / variation
Development and Regulatory status
Dec 20Available in the EU. £6,293.91 per 28-day pack containing 28 tezacaftor 50 mg/ivacaftor 75 mg fixed dose combination tablets .
Nov 20European Commission has granted approval of the label extension for tezacaftor/ivacaftor with ivacaftor .
Sep 20Recommended for EU approval by CHMP, in conjuction with approval of a new 50/75 mg tablet strength - the amended indication is "in a combination regimen with ivacaftor tablets for the treatment of patients with cystic fibrosis (CF) aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272‑26A→G, and 3849+10kbC→T" .
May 20Filed in the EU with a decision expected by Q4 2020 
Jun 19Approved in US .
Apr 19Has orphan drug status in EU & US .
Feb 19Vertex submitted an sNDA to the US FDA in late 2018 for tezacaftor/ivacaftor based on a previously completed Phase 3 safety study in children ages 6 through 11 years of age conducted in the U.S. and Canada. Vertex plans to file in the EU in H2 19 .
Fixed-dose combination of tezacaftor (a corrector modulator that enhances the number of channels of the CFTR protein at the cell surface) and ivacaftor.
CF is the most common inherited disease in white populations. Prevalence is 1 in 2,500 newborn infants, with calculated carrier frequency of 1 in 25. Just over 10,000 people were recorded as having CF in the 2013 UK CF Registry .
Cystic fibrosis, homozygous for F508del mutation in the CFTR gene OR heterozygous for F508del and a residual function (RF) mutation (F/RF), in patients aged 6 to 11 years
Trial or other data
PIII study to evaluate the efficacy of ivacaftor/tezacaftor in patients with CF aged 6 to 11 years, who are homozygous for the F508del mutation (F/F) or heterozygous for F508del with an eligible residual function mutation (F/RF). The trial will enrol 69 patients in Australia, Belgium, Denmark, Germany, Ireland, Switzerland, the UK, Poland and France. Primary outcome is absolute change in lung clearance index 2.5 at week 8; collection of these data is due to complete Dec 18 .
Results from the PIII study (NCT03559062) in 69 patients showed tezacaftor in combination with ivacaftor was well tolerated and safety data were consistent with previous studies. The study was designed to support a submission to the EMA to extend the indication of tezacaftor/ivacaftor to this patient population .
US licence was based on a PIII, initiated in Oct 16, that investigated the pharmacokinetics, safety and tolerability of ivacaftor in combination with tezacaftor (VX 661) in paediatric patients (6-11 years) with cystic fibrosis, homozygous or heterozygous for the F508del CFTR mutation (NCT02953314). It enrolled 70 patients in the US and Canada. Results from this trial showed that treatment was generally safe and well tolerated and safety data were consistent with those seen in previous PIII studies of tezacaftor/ivacaftor in children ages 12 and older .