Phase 1 and Phase 2 Study Results Find Potential Treatment for Severe Cystic Fibrosis

Vertex Pharmaceuticals recently announced positive data from phase 1 and 2 studies of 3 triple combination regimens in cystic fibrosis (CF) patients with one F508del mutation and one minimal function mutation (F508del/Min). These results are the first to present the potential of treating the underlying cause of those with difficult-to-treat CF.

Phase 2 studies of VX-152 and VX-440, both in combination with tezacaftor and ivacaftor, each included a group of patients with one F508del mutation and one minimal function mutation, and a group of those with 2 copies of the F508del mutation. Phase 2 results demonstrated mean absolute improvements in the percent predicted forced expiratory volume in one second (ppFEV₁) of 9.7 and 12 percentage points from the baseline for the triple combination regimens with VX-152 (200mg q12h) or VX-440 (600mg q12h).

The phase 1 study was a randomized, double-blind, placebo-controlled study that was intended to measure the safety and tolerability of single and multiple ascending doses of VX-659 alone and in triple combination with tezacaftor and ivacaftor in healthy participants. Data from the phase 1 study demonstrated a mean absolute improvement in ppFEV₁ of 9.6 percentage points from baseline for the triple combination regimen of VX-659, tezacaftor, and ivacaftor in patients with one F508del mutation and one minimal function mutation.

"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," said Jeffrey Chodakewitz, MD, 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."

Overall, the triple combination regimes were well tolerated among the studies since the majority of the adverse events were mild to moderate in severity. Vertex plans to continue development of the best triple combination regimen(s) for patients with CF.

"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 Rowe. "It's also encouraging to see that the addition of a next-generation corrector may lead to substantial additional benefits for patients with 2 copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor."