FDA issues Complete Response Letter relating to Kalydeco (ivacaftor) treatment of residal function mutations of Cystic Fibrosis transmembrane conductance regulator (CFTR). -Vertex

Vertex Pharmaceuticals Incorporated announced that it received a Complete Response Letter from the FDA for its supplemental New Drug Application (sNDA) for the use of Kalydeco (ivacaftor) in people with cystic fibrosis (CF) ages 2 and older who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The FDA determined that it cannot approve the application in its present form.

Kalydeco received the FDA's Breakthrough Therapy Designation in 2013, is currently approved in the U.S. to treat people with CF ages 2 and older who have one of 10 mutations in the CFTR gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H). As with the mutations for which Kalydeco is approved, this group of 23 residual function mutations is known to have some functional CFTR protein at the cell surface. This submission was also based on observed in vitro increases in chloride transport in response to ivacaftor in cells expressing CFTR. The presence of CFTR protein at the cell surface and increases in chloride transport are characteristics associated with clinical response to Kalydeco.

There are more than 1,500 people ages two and older with CF in the United States who have one of the 23 residual function mutations included in the sNDA. The 23 residual function mutations included in the sNDA are: 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+3A->G, E56K, P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G, E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, and D1270N.