FDA decision on Vertex's CF triple will come just ahead of planned CEO shakeup
Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.
FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.
Dubbed elexacaftor, the new drug is a “corrector” designed to fix the shape and course of defective CFTR protein, bringing more of them to the cell surface. Notably, tezacaftor has a similar function but does not address minimal function mutations. Meanwhile, ivacaftor is a “potentiator” that increases the function of the protein once it reaches the cell surface.
Ivacaftor is marketed on its own as Kalydeco, while Symdeko consists of both ivacaftor and tezacaftor.
An approval in March would mark a final victory for CEO Jeff Leiden, who has announced a surprise transition to the executive chairman role while passing the baton to current CMO Reshma Kewalramani in April 2020. Subsequent discussions on pricing would also draw attention to her negotiating style, given Vertex’s high profile confrontations with European single-payer systems.
“If approved, the VX-445 (elexacaftor), tezacaftor and ivacaftor triple combination regimen would be a significant advance in CF treatment as the first CFTR modulator for those with one F508del mutation and one minimal function mutation, and bring additional benefit to patients with two F508del mutations,” Kewalramani said in a statement.