‘Compelling’ mid-stage data for Vertex’ CF drugs

The results of two Phase II trials showed that combining each of the investigational therapies VX-440 and VX-152 with Kalydeco (ivacaftor) and tezacaftor induced dramatic 10 percentage-point improvements in ppFEV1 - a key measure of lung capacity - in patients with the condition who have one F508del mutation and one minimal function mutation.

Similarly, the group also presented findings of a Phase I trial showing the efficacy of experimental therapy VX-659 in combination with Kalydeco/tezacaftor in the same patient group, which are among the hardest to treat.

The safety profiles of the combinations also looked positive, having been were generally well tolerated across all three studies with the majority of adverse events mild to moderate in severity and discontinuation rates due to adverse events low.

VX-440, VX-152, and VX-659 are referred to as ‘correctors’ as they are designed to correct a malfunctioning protein in cystic fibrosis patients. These drugs are administered alongside another ‘corrector’ tezacaftor and Kalydeco, which raises levels of the corrected protein.

"Patients with minimal function mutations have been waiting for a medicine to treat the underlying cause of their disease, which makes these data showing pronounced improvements in lung function particularly important," said Professor Steven Rowe, director of the Gregory Fleming James Cystic Fibrosis Research Center amongst other positions, and co-chair of a steering committee of global CF experts and clinical trial investigators established by Vertex.

"It's also encouraging to see that the addition of a next-generation corrector may lead to substantial additional benefits for patients with two copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor."

"These safety and efficacy data are clear and compelling, indicating significant potential benefit for people with CF from each of these three different triple combination regimens," added Jeffrey Chodakewitz, executive vice president and chief medical officer at Vertex.

"We will be collecting and evaluating additional data from these and other studies and will make a decision on which regimen(s) to take forward into pivotal program(s), which we expect to begin in the first half of 2018."