Vertex Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) approved Symdeko (tezacaftor/ivacaftor and ivacaftor) as a therapy for cystic fibrosis (CF) patients carrying two copies of the F508del mutation in the CFTR gene (the gene defective in CF) or with one mutation that responds to tezacaftor/ivacaftor.
The therapy was approved for patients 12 years or older.
Vertex’s now has three approved therapies to treat the underlying cause of CF, and Symdeko is expected to be available at U.S. pharmacies starting this week.
“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,” Jeffrey Leiden, MD, Vertex’s chairman, president and CEO, said in a press release.
“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,” Leiden added.
Symdeko combines two active agents, VX-661 (tezacaftor) and ivacaftor (sold by Vertex as Kalydeco), to help improve the performance of the CFTR channel in CF patients. VX-661 helps the CFTR protein to move onto the cell surface, and once there, Kalydeco helps the CFTR ion channel to remain open for longer periods. Their combined action improves the balance of water and salts in affected organs, including the lungs.
Results of two Phase 3 studies, the EVOLVE (NCT02347657) and EXPAND (NCT02392234) trials, supported the FDA’s decision. The trials enrolled approximately 750 CF patients (12 years or older) carrying two copies of the F508del mutation, or with one F508del mutation and one mutation that impairs CFTR function.
Both studies showed that treatment with Symdeko significantly improved lung function and other health measures compared to placebo controls, with a favorable safety profile.
Patients who completed these Phase 3 studies were eligible to participate in an ongoing and open-label Phase 3 study, called EXTEND (NCT02565914), to evaluate the safety and efficacy of long-term treatment with Symdeko.
Vertex presented data from an early analysis showing that the initial improvements in lung function detected in the EVOLVE and EXPAND studies were maintained for up to 48 total weeks. EXTEND will also evaluate the improvements in lung function after a 96-week treatment, among other parameters.
“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,” said Patrick Flume, director of the Medical University of South Carolina Cystic Fibrosis Center and principal investigator for the EXTEND study.
“In particular, Symdeko is an important treatment option for patients who either never started or discontinued Orkambi [lumacaftor/ivacaftor], and it also provides increased benefit over Kalydeco alone for patients with residual function mutations,” Flume added.
The European Medicines Agency (EMA) is also evaluating the tezacaftor/ivacaftor combination for possible approval, and Vertex expects a decision in the second half of 2018.