Vertex plans to seek global regulatory approvals for either VX-659 or VX-445 triple combination regimen in both F/F and F/MF patient populations concurrently based on final 24-week data for both regimens expected in the second quarter of 2019.
Vertex Pharmaceuticals Incorporated announced that treatment with the triple combination of the next-generation corrector VX-445, tezacaftor and ivacaftor resulted in statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in two Phase 3 studies in people with cystic fibrosis (CF). Data from a pre-specified interim analysis of the Phase 3 study in people with one F508del mutation and one minimal function mutation showed a mean absolute improvement in ppFEV1 of 13.8 percentage points from baseline at week 4 of treatment compared to placebo (p<0.0001). In the Phase 3 study in people with two F508del mutations, the addition of VX-445 in patients already receiving tezacaftor and ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10.0 percentage points from baseline at week 4 of treatment compared to the control group in whom placebo was added to tezacaftor and ivacaftor (p<0.0001). The VX-445 triple combination regimen was generally well tolerated, and the safety and efficacy profile from the results released today supports the potential submission of a New Drug Application (NDA) for the VX-445 triple combination regimen.
The Phase 3 data announced recently for the VX-445 triple combination regimen follow Phase 3 data announced in late 2018 for the triple combination of VX-659, tezacaftor and ivacaftor that also showed a safety and efficacy profile supportive of a potential NDA submission. Given the similarity of the data for the 4-week primary efficacy endpoint for the VX-659 and VX-445 regimens and the near-term availability of the final 24-week data for both regimens in the second quarter of 2019, Vertex plans to utilize these final 24-week data to choose the best regimen to submit for regulatory approvals globally. Because these submissions will include the final 24-week data, Vertex will seek approval for patients ages 12 and older with one F508del mutation and one minimal function mutation and for patients with two F508del mutations concurrently. Vertex plans to submit an NDA to the U.S. FDA in the third quarter of 2019 and a Marketing Authorization Application (MAA) in Europe in the fourth quarter of 2019 for either the VX-659 or VX-445 triple combination regimen. The company also plans to disclose more detailed data from the Phase 3 studies of the selected triple combination regimen, including 24-week data from the study in patients with one F508del mutation and one minimal function mutation, in the second quarter of 2019.
Both the VX-659 and VX-445 triple combination regimens showed highly consistent and significant improvements in lung function across our Phase 3 programs, underscoring the important clinical benefit that a triple combination regimen may provide to patients with two F508del mutations and to those with one F508del and one minimal function mutation. We look forward to submitting global regulatory applications for one of these triple combination regimens for both patient populations later this year,
said Reshma Kewalramani,
M.D., Executive Vice President,
Global Medicines Development and
Medical Affairs and Chief Medical Officer at Vertex.