Vertex Scores FDA Nod for CF Combo Drug, Sets $292,000 Price Tag

The U.S. Food and Drug Administration (FDA) approved Vertex Pharmaceuticals’ Symdeko (tezacaftor/ivacaftor and ivacaftor) for cystic fibrosis (CF) in patients ages 12 and older with two copies of the F508del mutation.

Kalydeco (ivacaftor) is Vertex’s medication for CF. Symdeko is a combination of Kalydeco and tezacaftor/ivacaftor. It has been specifically approved for patients with two copies of the F508del mutation found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, or in patients with at least one mutation that is responsive to tezacaftor/ivacaftor.

“Today is an exciting day for the CF community,” said Jeffrey Leiden, Vertex’s chairman, president and chief executive officer, in a statement. “The approval of Symdeko, our third disease-modifying CF medicine, offers many patients an important new treatment option. This approval is an important milestone in our journey to treat every person with CF, and we remain committed to urgently advancing our efforts to develop new medicines that treat the underlying cause of CF for the many people still waiting.”

The combination is also being evaluated by the European Medicines Agency (EMA) and a decision is expected in the second half of the year.

The cause of CF is a defective or missing CF transmembrane conductance regulator protein. This is caused by mutations in the CFTR gene. To have CF, children inherit two defective CFTR genes, one from each patient. Approximately 2,000 CFTR gene mutations have been identified. The mutations result in not enough CFTR proteins or proteins that don’t function properly. It results in poor flow of salt and water into and out of the cell in several organs. This leads to an accumulation of abnormally thick, sticky mucus in the lungs, which can cause chronic lung infections and progressive lung damage that often leads to death. For patients with CF, the median age of death is the mid-to-late 20s.

Reuters notes, “Vertex shares rose about 2 percent to $154.92 in extended trading after the approval was announced about two weeks ahead of an expected FDA action date. The treatment, which will be sold under the brand name Symdeko, adds the new drug tezacaftor to previously approved Kalydeco (ivacaftor) and is expected to form the backbone of eventual triple combinations that could treat up to 90 percent of patients with the disease that leads to serious lung infections and deteriorating lung function.”

Symdeko will be priced at about $292,000.

The company is in the process of developing two different triple combination therapies for CF. On February 1, Vertex announced it had chosen two next-generation correctors, VX-659 and VX-445, to move into Phase III development as part of the triple combinations. They were based on initial Phase II data.

Once discussions with the FDA are completed, the company expects to launch a Phase III trial in mid-2018 to evaluate VX-445 in triple combination with tezacaftor and VX-561 as a once-daily regimen. In early trials, the triple combination therapies were generally well tolerated and adverse events were mostly mild to moderate.

“These results support the selection of both the VX-659 and VX-445 triple combination regimens and underscore the potential for these regimens to provide significant clinical benefits for up to 90 percent of people with CF,” said Jeffrey Chodakewitz, executive vice president and chief medical officer of Vertex, in a statement. “We look forward to concluding our discussions with regulators and initiating Phase III development in the first half of the year, with the goal of bringing a triple combination regimen to patients as quickly as possible.”