Vertex has picked the two next-generation correctors it will advance into phase 3 cystic fibrosis trials. VX-659 and VX-445 landed spots in experimental triple combinations designed to treat 90% of cystic fibrosis patients after delivering strong efficacy data in midphase trials.
Boston-based Vertex has spent the past six months going over data on four drugs that could slot into its triple combination. All four candidates impressed in midphase trials—earlier data from trials of VX-152, VX-440 and VX-659 sent Vertex’s stock up 26%—but in the end two of the assets shone a little brighter than the rest.
VX-659 and VX-445 both increased FEV1, a measure of lung function, by more than 13%. That is one to three percentage points more than VX-152 and VX-440 managed. More strikingly, it exceeds the improvements achieved by Vertex’s Kalydeco in a subpopulation of cystic fibrosis patients.
If VX-659 or VX-445 can replicate the performance in phase 3, Vertex will have a combination therapy that brings Kalydeco-like improvements in lung function to most cystic fibrosis patients. That would make a major difference to the lives of many of the 30,000 people in the U.S. who live with the lung condition. And result in a major new revenue source for Vertex.
Vertex is currently putting together a phase 3 program designed to get it to that point. Talks with regulators about a combination of VX-659, tezacaftor and Kalydeco are underway. Vertex hopes to start a phase 3 program featuring that cocktail in the first half of the year.
Beyond that, Vertex is working to get a combination of VX-445, tezacaftor and the Kalydeco-like VX-561 into phase 3 around the middle of the year. The start of that trial is dependent on data from a midphase trial of the combination.
The anticipated start dates for the phase 3 programs give Vertex a clear lead over potential rivals for the triple-combination market. AbbVie is working with Galapagos on similar combinations to those in development at Vertex but is yet to post clinical data on the complete cocktail. Galapagos expects to share data on its first triple-combination candidate around the middle of the year.