FDA Approves Symdeko to Treat the Underlying Cause of Cystic Fibrosis

Drug maker Vertex has announced that the FDA has approved tezacaftor/ivacaftor and ivacaftor (Symdeko) for the treatment of the underlying cause of cystic fibrosis (CF) in patients aged 12 or older who have 2 copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, or who have at least 1 genetic mutation that is responsive to treatment with tezacaftor/ivacaftor.

CF is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. There are approximately 2000 known mutations of the gene, some of which result in a CFTR protein that presents with abnormal folding within the cell, which prevents it from reaching the cell surface. The newly approved drug works by using tezacaftor to address the trafficking and processing defect of the CFTR protein to allow it to reach the cell surface, where ivacaftor can increase the amount of time that the protein stays open.

“Today is an exciting day for the CF community. The approval of Symdeko, our third disease-modifying CF medicine, offers many patients an important new treatment option,” said Jeffrey Leiden, MD, PhD, Vertex's chairman, president, and CEO, in a statement.

Currently approved treatments for CF include Vertex’s ivacaftor (Kalydeco), which is also approved to treat children aged 6 and older, and ivacaftor/lumacaftor (Orkambi), which, like Symdeko, is approved to treat patients aged 12 and older. Symdeko’s list price will be $292,000 per patient per year (compared with Kalydeco’s list price of $311,000 and Orkambi’s list price of $272,000).

Vertex is also in the process of finalizing phase 3 studies for 2 additional drug candidates, VX-659 and VS-445, with the eventual goal of bringing a triple-combination regimen to market. Vertex plans to initiate a phase 3 program in the first half of 2018 to evaluate VX-659 in combination with tezacaftor and ivacaftor, and a mid-2018 phase 3 program evaluating VX-445 in combination with tezacaftor and an additional drug candidate, VX-561, as a once-daily regimen.

Both combinations, says Vertex, were generally well tolerated in phase 2 studies, with a low rate of discontinuation due to adverse events.