EU approves Symveki + Kalydeco for cystic fibrosis F508del mutation.- Vertex.

The EU has approved Symveki (tezacaftor 100mg + ivacaftor 150mg) in a combination regimen with Kalydeco (ivacaftor 150mg) to treat a particular subgroup of patients with cystic fibrosis. The combination is approved for use in patients aged 12 and older who either have two copies of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene, or one copy of the F508del mutation and a copy of one of the 14 mutations in which the CFTR protein shows residual activity (P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A-G, S945L, S977F, R1070W, D1152H, 2789+5G-A, 3272-26A-G, and 3849+10kbC-T).

Approval is based on data from two pivotal Phase III studies, EVOLVE and EXPAND, published in the New England Journal of Medicine in 2017. Results revealed that Symveki in combination with Kalyedeco gave benefits across different populations of CF patients, including significant improvements in lung function, with a generally well tolerated safety profile and a lack of adverse events.

The overall safety profile of Symdeko is based on data from three double-blind, placebo-controlled, Phase III clinical trials: 2 parallel-group trials of 12 and 24 week duration and one cross-over design trial of 8 weeks duration. Eligible patients were also able to participate in an open-label extension safety study (up to 96 weeks of Symdeko). In the three placebo-controlled Phase III trials (Trials 1, 2 and 3), a total of 496 patients with CF aged 12 years and older received at least one dose of Symdeko. The proportion of patients who discontinued study drug prematurely due to adverse events was 1.6% for Symdeko-treated patients and 2.0% for placebo-treated patients. Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in Symdeko-treated patients compared to placebo included distal intestinal obstruction syndrome, 3 (0.6%) Symdeko -treated subjects vs. 0 placebo. There were no deaths in the placebo controlled trials, and one death in the open label extension study due to respiratory failure and influenza infection in a patient who had discontinued Symdeko seven weeks prior. The safety profile of Symdeko was generally similar across all subgroups of patients, including analysis by age, sex, baseline percent predicted FEV1 and geographic regions.