Triple combination regimens for next generation treatment of cystic fibrosis.

Vertex Pharmaceuticals Incorporated announced the selection of two next-generation correctors, VX 659 and VX 445, to advance into Phase III development as part of two different triple combination regimens for people with cystic fibrosis (CF). The decision to advance VX 659 and VX 445 into Phase III development was based on initial Phase II data, including new data from ongoing Phase II studies that showed mean absolute improvements in percent predicted forced expiratory volume in one second (ppFEV1) of up to 13.3 and 13.8 percentage points from baseline through four weeks of treatment for the triple combination regimens with VX 659 (400mg QD) or VX 445 (200mg QD), respectively, in people who have one F508del mutation and one minimal function mutation (F508del/Min).

Regulatory discussions are ongoing to finalize the design of Phase III programs for VX 659 and VX 445. Upon completion of these discussions, Vertex plans to initiate a Phase III program in the first half of 2018 to evaluate VX 659 in triple combination with tezacaftor and ivacaftor. In addition, the company plans to initiate a Phase III program in mid-2018 to evaluate VX 445 in triple combination with tezacaftor and VX 561 as a once-daily regimen, pending additional data in the first half of 2018, including the Phase II data on the combination of VX 445, tezacaftor and VX 561.

The triple combination regimens were generally well tolerated across both studies, and the majority of adverse events were mild to moderate in severity. Across the studies, the discontinuation rate due to adverse events was low.