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Study Status: Fully enrolled and data anticipated mid 2014. A second corrector further enhances in vitro F508del CFTR function. F508del/F508del. F508del/G542X. Kindly provided by Vertex Pharmaceuticals, Inc. Strategic planning for back-up correctors began 4 years go.
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A second corrector further enhances in vitro F508del CFTR function F508del/F508del F508del/G542X Kindly provided by Vertex Pharmaceuticals, Inc.
Strategic planning for back-up correctors began 4 years go • Reviewed lessons learned from first generation correctors • Created road map for more robust second generation compounds • Strong partners in place • Amazing progress • Novel screens developed • Up to 6 million compounds will be reviewed
How Much CFTR is Enough?The Ivacaftor – G551D Benchmark Study Baseline 150 mg Adapted from Accurso et al New Engl J Med 2010
FEV1 % Predicted Absolute Change from Baseline Treatment effect through Week 24 + 10.6 % P < 0.0001 Treatment effect through Week 48 + 10.5 % P < 0.0001 Ramsey et al., N Engl J Med. 2011 Nov 3;365(18):1663-72
Change from Baseline in Sweat Chloride Treatment effect through Week 24 – 47.9 mmol/L P < 0.0001 Treatment effect through Week 48 – 48.1 mmol/L P < 0.0001 Ramsey et al., N Engl J Med. 2011 Nov 3;365(18):1663-72
The ivacaftor effect persists for many months Open Label Follow-On See: McKone et al. NACFC 2013 Poster #227
Effect of 150 mg BID ivacaftor on hospitalization rate in G551D patients From the GOAL presentation and kindly provided by S. Rowe
Ivacaftor coverage of other gating mutations • In vitro studies have shown that ivacaftor improves chloride transport in CF cells with other CFTR gating mutations1 • G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, G1349D, S1255P • KONNECTION Study: Blinded, placebo-controlled 8 week crossover study of ivacaftor in other CFTR gating mutations with open label extension2 • At 8 weeks, FEV1 change from baseline favored ivacaftor treatment by 10.7% predicted (P < .0001) • Comparable to ivacaftor treatment effect seen at 24 weeks in G551D patients (10.6% predicted, P < .0001) Study Status: Crossover portion complete, supplemental New Drug Application filed 1- Yu et al. J Cyst Fibros. 2012;11(3):237-45. 2- DeBoeck et al. NACFC 2013 Symposium 3.15 and Poster #241 Kindly provided by Vertex Pharmaceuticals