Cystic fibrosis (CF) patients in Australia age 12 and older, who have two copies of the F508del mutation in the CFTR gene (a copy inherited from each parent), now can be treated with Vertex Pharmaceuticals’ Symdeko (tezacaftor/ivacaftor and ivacaftor).
The treatment also was approved for any mutation in the CFTR gene that responds to Symdeko based on lab tests and/or clinical evidence. Some of the treatment-responsive mutations are: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, 3849+10kbC→T, E56K, R74W, D110E, D110H, E193K, E831X, F1052V, K1060T, A1067T, F1074L, and D1270N.
CF patients who don’t know their gene mutation may want to consult their healthcare provider to learn if they have a Symdeko-sensitive mutation.
“We are delighted that the Therapeutic Goods Administration in Australia recognized the safety profile and efficacy of Symdeko. This approval brings us one step closer to our future goal of bringing treatment to all people living with CF,” Reshma Kewalramani, MD, said in a press release. Kewalramani is executive vice president and chief medical officer at Vertex.
“This new medicine is an especially important treatment option for patients with residual function mutations and those with two copies of the F508del mutation who either never started or discontinued Orkambi (lumacaftor/ivacaftor),” Kewalramani added.
Symdeko is a combination of tezacaftor (VX-661) and ivacaftor (sold by Vertex under the brand name Kalydeco). This combination therapy was designed to resolve the impaired activity of the CFTR protein caused by several genetic mutations linked to CF.
The approval was based on clinical data from the EVOLVE (NCT02347657) and EXPAND (NCT02392234) Phase 3 trials. Combined, the studies enrolled more than 700 CF patients, age 12 and older, who had two copies of the F508del mutation, or who had one F508del mutation and a second mutation predicted to be responsive to the combo therapy.
Results from both Phase 3 studies showed that Symdeko led to clinically meaningful improvements in lung function, compared to Kalydeco alone, as shown by a significantly absolute change from the beginning of the study (baseline) in percent predicted forced expiratory volume in one second (ppFEV1) — a measure of how much air can be exhaled in one second after a deep inhaled breath.
In the EVOLVE trial, patients treated with the Symdeko had a difference of 4.0% in ppFEV1 compared to placebo controls; while in the EXPAND trial this difference was 6.8%.
Also, patients in the EVOLVE trial treated with the combo therapy had a 35% reduction in the annualized rate of pulmonary exacerbations, compared to those in the placebo group.
Participants who completed the Phase 3 studies were eligible to continue treatment with Symdeko in the 96-week open-label EXTEND Phase 3 rollover study (NCT02565914), which is ongoing.
An interim analysis of the EXTEND trial confirmed the therapy’s safety profile and effectiveness seen in previous trials — patients’ improvement in lung function also were maintained up to 48 weeks.