Orkambi ivacaftor/lumacaftor regulatory update

FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that available efficacy and safety data support approval of Orkambi lumacaftor/ivacaftor from Vertex to treat cystic fibrosis in patients ages >=12 who are homozygous for the F508 mutation in the CF transmembrane conductance regulator ( CFTR) gene. Orkambi has breakthrough therapy designation from FDA and is under Priority Review, with a July 5 PDUFA date.

Last summer, Vertex said Kalydeco ivacaftor plus lumacaftor ( VX-809) met the primary endpoint of improving the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at week 24 vs. placebo in the identical Phase III TRAFFIC and TRANSPORT trials in the population (see BioCentury, June 30, 2014). While some panel members were initially concerned about whether a 2.6-3% improvement on ppFEV1 was clinically meaningful, the concerns were addressed by CF patients, Vertex and physicians who treat CF, including several who were on the committee. All highlighted the importance of any improvement in lung function in a patient population that typically loses 1-3% of lung function annually. They also highlighted the importance of the improvement on secondary endpoints, particularly BMI and pulmonary exacerbations, which lead to permanent loss in lung function. ...