Vertex Pharmaceuticals’ Symkevi (tezacaftor/ivacaftor) is one step closer to being approved in the European Union as a treatment for cystic fibrosis (CF) patients ages 12 or older who have certain CFTR genetic mutations.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of the combo therapy Symkevi plus Kalydeco (ivacaftor) for patients who have two copies of the F508del mutation, or one copy of this CFTR gene variant plus one of the following 14 residual mutations: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.
“Our goal at Vertex is to find a cure for all people living with CF and we are moving rapidly towards treating up to 90 percent of patients,” Reshma Kewalramani, MD, executive vice president of global medicines development and medical affairs and chief medical officer at Vertex, said in a press release. “Today’s announcement is a pivotal accomplishment along that journey.”
If the European commission grants marketing authorization to this new therapy, Symkevi will be made available as film-coated tablets containing 100 mg of tezacaftor (VX-661) and 150 mg of ivacaftor, which should be given in combination with Kalydeco. Symkevi should be taken in the morning and Kalydeco alone in the evening.
Upon approval, Symkevi will become Vertex’s third medicine available in Europe to treat the CFTR protein defect in CF patients.
CHMP’s positive opinion was supported by clinical data from two randomized, double-blind Phase 3 trials, EVOLVE (NCT02347657) and EXPAND (NCT02392234). The studies enrolled about 750 patients with CF, ages 12 and older, who had either two copies of the F508del mutation, or one F508del mutation plus a CFTR mutation predicted to be responsive to Symkevi.
Data from both studies showed that the combo therapy promoted clinically meaningful improvements in lung function compared with Kalydeco alone, as determined by changes in percent predicted forced expiratory volume in one second (ppFEV), a measure of lung function. Additionally, patients in the EVOLVE trial treated with the combo therapy had a 35% reduction in the annualized rate of pulmonary exacerbations compared with those in the placebo group.
Patients who completed these Phase 3 studies were eligible to enroll in an ongoing, open-label trial, called EXTEND (NCT02565914), to evaluate the safety and effectiveness of long-term use of the combo therapy.
During the trials, the most common adverse events reported were headache and inflammation and irritation of the nasal passages and the back of the throat (nasopharyngitis).
“Tezacaftor/ivacaftor combination therapy for CF is another important achievement in the development of disease modulating therapies,” said Stuart Elborn, MD, clinical professor of respiratory medicine and director of the adult CF center at the Royal Brompton Hospital in London. “This combination improves important clinical outcomes and may benefit those who cannot use Orkambi (lumacaftor/ivacaftor).”