The US Food and Drug Administration (FDA) has rejected Vertex Pharmaceuticals‘ supplemental new drug application (sNDA) for Kalydeco (ivacaftor) designed to treat people with cystic fibrosis (CF) aged two and older, with one of 23 residual function mutations in the CF transmembrane conductance regulator (CFTR) gene.

The company received a complete response letter from the FDA, which stated that the agency cannot approve the sNDA in its current form.

In order to determine an appropriate path forward for the approval of the drug, the company plans to meet with the FDA.

The sNDA was based on preclinical data for ivacaftor in residual function mutations, the established clinical profile of Kalydeco and on previously reported data from an exploratory Phase IIa trial.

"Our intention with this submission was to rapidly bring Kalydeco to additional people with CF who we believe may benefit."

The company noted that in 19 of the 24 patients enrolled in this trial, eight of the 23 mutations proposed in the sNDA were represented.

Vertex 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 chose to pursue this approach given our strong belief in the science of CF, and in the well-established safety of Kalydeco across many different groups of people with CF.

"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."

CF is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene and it results in poor flow of salt (chloride) and water into and out of the cell in a number of organs, including the lungs.

In 2013, the FDA granted breakthrough therapy designation for Kalydeco and is currently approved in the US to treat people with CF ages two and older who have one of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H mutations in their CFTR gene.

The company noted that Kalydeco 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.