In Vitro Study Results: In Vitro Analysis of
KALYDECO® (ivacaftor)1,2

The in vitro effect of ivacaftor on CFTR activity in certain mutations was evaluated1,2

  • Using in vitro lab experiments, cell lines were modified to produce mutant forms of CFTR protein
  • CFTR-mediated chloride transport was measured in these cell lines before and after exposure to ivacaftor

KALYDECO improved chloride transport by more than or equal to the 10% threshold in 33 mutations2


aA46D, G85E, E92K, P205S, R334W, R347P, T338I, S492F, I507del, V520F, A559T, R560S, R560T, A561E, L927P, H1054D, G1061R, L1065P, R1066C, R1066H, R1066M, L1077P, H1085R, M1101K, W1282X, and N1303K mutations are not responsive to ivacaftor potentiation, based on the in vitro CFTR chloride response threshold.2


A net increase of at least 10% of normal over baseline in chloride transport is reasonably expected to predict clinical benefit1,2,*

  • An increase of 10% of normal in CFTR activity was the threshold for response
  • The 10 previously approved mutations all exceeded the 10% in vitro threshold with clinical effects demonstrated in clinical trials
  • The 23 additional mutations exceeded the 10% in vitro threshold
  • Magnitude of in vitro response does not necessarily predict magnitude of clinical benefit

*When CFTR function is ≤10% of normal (ie, functioning at a loss of at least 90%), manifestations of CF disease can be seen. As such, a net increase of ≥10% of normal CFTR function is predictive of clinical benefit in patients with certain CFTR mutations.3


KALYDECO was approved for an additional 23 mutations in May of 2017, based on responsiveness to KALYDECO demonstrated in this assay.2,4,†

11 of these 23 mutations have clinical data.

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