Vertex Pharmaceuticals (Europe) Limited, today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for SYMKEVI® (tezacaftor/ivacaftor) in a combination regimen with ivacaftor (KALYDECO®) for the treatment of people with cystic fibrosis (CF) aged 12 and older who either have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, or one copy of the F508del mutation and a copy of one of the following 14 mutations in which the CFTR protein shows residual activity: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.
If granted Marketing Authorization by the European Commission (EC), tezacaftor/ivacaftorwill be used in combination with ivacaftor and will be the first medicine to treat the CFTR protein defect in CF patients who have one copy of the F508del mutation and a copy of one of 14 mutations that result in residual CTFR activity. It also provides a new treatment option for a significant number of people living with CF who have two copies of the F508del mutation.
“Our goal at Vertex is to find a cure for all people living with CF and we are moving rapidly towards treating up to 90 percent of patients,” said Reshma Kewalramani, MD, Executive Vice President, Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex. “Today’s announcement is a pivotal accomplishment along that journey. If approved, tezacaftor/ivacaftor in combination with ivacaftor represents an important option for people with two copies of the F508del mutation and the first medicine in the EU for patients with one copy of the F508del mutation and a copy of one of 14 mutations that result in residual CTFR activity.”
The regulatory submission was supported by results from two pivotal Phase 3 studies, EVOLVE and EXPAND, published in the New England Journal of Medicine in November 2017. Results showed treatment with tezacaftor/ivacaftor in combination with ivacaftor provides benefits across different CF populations, including statistically significant improvements in lung function, as determined by absolute change from baseline in ppFEV1, and with a generally well tolerated safety profile and a lack of increased respiratory adverse events compared to placebo. The most common adverse reactions experienced by patients who received tezacaftor/ivacaftor in combination with ivacaftor in pooled, placebo-controlled Phase 3 studies were headache and nasopharyngitis.
“Tezacaftor/ivacaftor combination therapy for CF is another important achievement in the development of disease modulating therapies. This combination improves important clinical outcomes and may benefit those who cannot use ORKAMBI® (lumacaftor/ivacaftor),” said Professor Stuart Elborn, Clinical Professor of Respiratory Medicine, and Centre Director for Specialist Adult Cystic Fibrosis at the Royal Brompton Hospital, London.
Tezacaftor/ivacaftor in combination with ivacaftor was approved by the U.S. Food and Drug Administration (FDA) in February 2018 and by Health Canada in June 2018. It is marketed as SYMDEKO™ in the U.S. and Canada.