RARE Daily

Report of Patient Deaths Creates Questions about Vertex’s CF Drug

August 29, 2019

Marie Daghlian

Thirty patients have died after taking a recently approved Vertex Pharmaceuticals therapy for cystic fibrosis, according to the U.S. Food and Drug Administration’s database of adverse side effects.

The drug, Symdeco (tezacaftor/ivacaftor and ivacaftor), was approved in June for use in children with cystic fibrosis ages 6 through 11 years with a specific mutation.

The reports of death are usually submitted to the database by healthcare professionals and are often incomplete as to exactly how the patient died and whether or not other medications were involved. According to a report in STAT, Vertex issued a statement saying it has no evidence linking the deaths to Symdeko and that it has not received any communication from the FDA about the safety of the drug.

In a statement to STAT, Vertex said it has no evidence linking the use of Symdeko with the reported deaths and that it has received no communication from the FDA about the drug’s safety.

Cystic fibrosis (CF) is a rare, life-shortening genetic disease caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes—one from each parent—to have CF. There are approximately 2,000 known mutations in the CFTR gene.

Some of these mutations, which can be determined by a genetic testing, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death, usually in the mid-to-late 20s.

The approval of Symdeco covers children who have two copies of the F508del-CFTR mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeco. The FDA had previously approved it for use in patients with cystic fibrosis 12 years and older with two copies of the F508del mutation or one copy of a responsive mutation.

Symdeco’s approval was based on a completed a 24-week phase 3 open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of tezacaftor/ivacaftor and ivacaftor in children ages 6 through 11 years in the United States and Canada. The regimen was generally well tolerated, and safety data were similar to what was observed in previous studies of patients aged 12 years and older. The full data from this study will be published later this year.

Symdeco is one of several cystic fibrosis treatments discovered by Vertex through its collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Symdeco is also already approved in Canada, Switzerland, Australia, and the European Union for the treatment of CF in patients ages 12 years and older with certain mutations. Vertex plans to submit an application for the use in patients ages 6 through 11 years in the European Medicines Agency in the second half of 2019.

Symdeco is also the backbone of a new drug application Vertex just submitted to the FDA for a triple combination of elexacaftor, tezacaftor, and ivacaftor as a treatment for CF patients with two F508del mutations.

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