The agency sent a complete response letter to Vertex, stating that it cannot approve the company’s supplemental new drug application (sNDA) in its current form.
Vertex plans to meet with the FDA to identify on how to go ahead with the development.
Vertex Pharmaceuticals executive vice president and chief medical officer Jeffrey Chodakewitz said: "Our intention with this submission was to rapidly bring Kalydeco to additional people with CF who we believe may benefit.
"We are disappointed by this decision and look forward to discussing with the FDA the next steps to bring Kalydeco to people with CF who have these residual function mutations."
The sNDA was based on preclinical data for ivacaftor in residual function mutations, the established clinical profile of Kalydeco and on earlier reported data from an exploratory phase 2a trial.
Vertex said in 19 of the 24 patients enrolled in the study, eight of the 23 mutations proposed in the sNDA were represented.
Kalydeco is a prescription medicine used to treat CF in patients age 2 years and older who have any of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutations in their CF gene.
It is not for use in people with CF due to other mutations in the CF gene and is not effective in patients with CF with two copies of the F508del mutation (F508del/F508del) in the CF gene.