FDA Clears Tezacaftor/Ivacaftor Combo for Cystic Fibrosis

Megan Brooks


February 13, 2018

The US Food and Drug Administration (FDA) has approved a third drug from Vertex Pharmaceuticals directed at an underlying cause of cystic fibrosis (CF), the company has announced.

The new treatment combines ivacaftor (Kalydeco), approved in 2012, with tezacaftor. It will be sold under the brand name Symdeko. In 2015, Vertex's combination of lumacaftor and ivacaftor (Orkambi) became the first drug approved by the FDA to treat the underlying cause of CF.

Symdeko is indicated for the treatment of CF in people aged 12 years and older who have two copies of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor.

Vertex said it would start shipping Symdeko to pharmacies in the United States this week.

CF is a rare, life-shortening genetic disease that affects approximately 75,000 people in North America, Europe, and Australia. The disease is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene.

Ivacaftor enhances the function of the CFTR protein once it reaches the cell surface to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. Tezacaftor increases the amount of mature CFTR at the cell surface by targeting the processing and trafficking defect of the CFTR protein.

The tezacaftor/ivacaftor combination was assessed in two phase 3 studies (EVOLVE and EXPAND) that involved about 750 people with CF. Patients were aged 12 years and older and had two copies of the F508del mutation or one F508del mutation and one mutation that results in residual CFTR function.

"Across both studies, patients treated with Symdeko experienced statistically significant and clinically meaningful improvements in lung function and other measures of disease, with a favorable safety profile," the company said in a news release.

Early data from the ongoing EXTEND rollover study show that improvements in lung function and the safety and tolerability profiles seen in EVOLVE and EXPAND were sustained for up to 48 total weeks of treatment with Symdeko, the company notes.

"We've already seen the significant impact that disease-modifying medicines can have on patients and are incredibly pleased that there is now a third treatment option that enables more patients to benefit from CFTR modulation," Patrick Flume, MD, director of the Medical University of South Carolina Cystic Fibrosis Center and principal investigator for the EXTEND study, said in the news release.

"In particular, Symdeko is an important treatment option for patients who either never started or discontinued Orkambi, and it also provides increased benefit over Kalydeco alone for patients with residual function mutations," said Flume.

Vertex Pharmaceuticals said it expects that Symdeko will be approved in the European Union later this year.

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