In the wake of recent promising clinical results, Vertex Therapeutics announced the submission of a supplemental New Drug Application to the U.S. Food and Drug Administration for the approval of the drug Kalydeco (ivacaftor) for patients with cystic fibrosis who are more than 18 years old and present with the R117H mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The drug is already used in the United States to treat CF patients who are more than six years old and who have one of nine different gene mutations.
“This submission is another step forward in our goal to help more people with this devastating disease,” said Jeffrey Chodakewitz, M.D., Senior Vice President and Chief Medical Officer at Vertex. “While people with the R117H mutation exhibit a wide range in the severity of their disease, their lung function often declines as they get older, marking the need for new medicines.”
In order to enroll this submission, Vertex performed a Phase 3 study of ivacaftor, which included 69 CF patients who were more than six years old and had at least one R117H mutation. The study wasn’t able to determine the absolute change from baseline in ppFEV1 (percent predicted forced expiratory volume in one second) for ivacaftor compared to placebo. However, the results demonstrated that patients more than 18 years old saw lung function improve significantly along with other key secondary endpoints.
The subset analysis performed to confirm the data included 50 CF patients with a mean baseline absolute FEV1 of 65 percent predicted. All patients revealed an average improvement of 5.0 percentage points in ppFEV1, through 24 weeks of treatment. A decrease in sweat chloride and improvements in CFQ-R was also observed. The safety and tolerability of the drug is similar to the one tested in previous Phase 3 studies for Kalydeco. Adverse events may include infective pulmonary exacerbation, cough, and headache.
Kalydeco is used currently in patients with the G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D mutations. The drug is not effective in patients with CF with 2 copies of the F508del mutation in the CFTR gene, and its safety in children with CF younger than 6 years of age has not been established. CF is a genetic disorder that affects about 300 people in the United States and is caused by a defective or missing CFTR protein that results from mutations in the CFTR gene.
The company also expressed its intention to submit a Marketing Authorization Application in Europe in the third quarter of 2014 for people with CF aged 18 or older and with the R117H mutation in the CFTR gene. The drug was recently recommended for approval by the European Committee for Medicinal Products for Human Use (CHMP), which may mean treatment for hundreds of people with specific non-gating mutations.