FDA, EMA Accept Tezacaftor-Kalydeco Combo for Priority Review

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have accepted for priority review applications for a combination of tezacaftor and Kalydeco (ivacaftor) as treatment for a subset of cystic fibrosis (CF) patients, Vertex Pharmaceuticals announced.

“If approved, the tezacaftor/ivacaftor combination treatment would become Vertex’s third medicine to treat the underlying cause of cystic fibrosis, offering an important new treatment option for a large group of patients with this rare and life-shortening disease,” Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex, said in a press release.

“We look forward to working with the agencies to facilitate a rapid review of these applications,” Chodakewitz added.

The combination of tezacaftor and Kalydeco is indicated for CF patients 12 years or older carrying one of the following gene mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: two copies of the F508del mutation, or one F508del mutation and one residual function mutation that is responsive to the tezacaftor-Kalydeco treatment.

The applications were based on positive results from previous Phase 3 clinical trials — the EVOLVE (NCT02347657) and the EXPAND (NCT02392234) studies — that showed that combining tezacaftor with Kalydeco significantly improved lung function in CF patients carrying either one or two copies of the F508del mutation in the CFTR gene.

In CF patients with the F508del mutation, the CFTR protein is abnormal (its folding is not correctly processed) and as a consequence, the protein does not reach the cells’ surface where it is required. Tezacaftor addresses the underlying issue of the defective protein and allows it to reach the cell surface, whereas Kalydeco enhances CFTR protein function.

In the U.S., the FDA granted priority review to the tezacaftor-Kalydeco combination, shortening the time for the regulatory process from 12 months to eight months. An action date is now set for Feb. 28, 2018. Additionally, the new combo has received breakthrough therapy designation, which expedites the development and review of drugs for serious conditions.

In Europe, a marketing authorization application was validated, meaning that submission is complete and ready for review by the Committee for Medicinal Products for Human Use (CHMP). The European Commission, which decides whether to approve a therapy’s commercialization in the EU, will make a final decision taking into account the CHMP’s opinion.