Vertex’s Phase II triple combos spurs optimism for F508del homozygous CF patients, heterozygous group draws pause - experts

11 Jul 2017

Vertex Pharmaceutical’s (NASDAQ:VRTX) triple combinations of a CFTR potentiator and two correctors elicited expert optimism for Phase II due to encouraging preclinical rationale for F508del homozygous and F508del/minimal CFTR function heterozygous patients, albeit with caution in the latter.

Vertex’s triple combination effort consists of two Phase II cystic fibrosis trials with: CFTR potentiator Kalydeco (ivacaftor)/CFTR corrector VX-661 (tezacaftor) and either of the next-generation correctors -- VX-152 (NCT02951195) or VX-440 (NCT02951182) -- in F508del mutation homozygous patients and F508del mutation/minimal CFTR function heterozygous ones.

Experts were buoyed by the potential of triple combinations due to the idea that adding another effective corrector to a potentiator/corrector combo could help in overcoming misfolding of the CFTR protein and result in a greater improvement in FEV1 (lung function). This would aid the CFTR potentiating action of Kalydeco – increasing CFTR protein activity on gating defects on the cell surface. With no major obvious differentiators, optimism for both VX-152 and VX-440, was also rooted in preclinical efficacy data and the fact that preclinical CF models have done fairly well in predicting success with Vertex’s other CF drugs, said experts.

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