Tezacaftor/Ivacaftor: Promising Results from Phase 3 Clinical Trials

Tezacaftor/Ivacaftor: Promising Results from Phase 3 Trials

Results released from the first of the large Phase 3 clinical trials of the drug combination Tezacaftor/ivacaftor demonstrated that people with CF with two copies of the F508del mutation ages 12 and older who received the treatment had significant improvements in lung function (4 percentage points compared to placebo) and in other key measures of the disease, including exacerbations (sudden worsening of symptoms) and quality of life.

Tezacaftor/ivacaftor was well tolerated, with an overall incidence of side effects similar to that seen in the placebo treated group. Additionally, respiratory complications were similar between placebo and treatment groups.

The 24-week study was conducted at over 90 clinical trial sites in North America and Europe. In total, more than 500 people with two copies of the F508del mutation, ages 12 and older participated in the study.

The second of the Phase 3 clinical trials tested the safety and effectiveness of tezacaftor in combination with ivacaftor for people with one F508del mutation and a second CFTR mutation that results in residual function.

The eight-week study showed that, compared with those on placebo, participants with one F508del and one residual function mutation who took the combination treatment improved lung function by 6.8 percentage points. The study also tested ivacaftor without tezacaftor. Participants who only received ivacaftor had a 4.7 percent improvement in lung function compared to placebo.

The residual function mutations eligible for inclusion in the residual function trial were chosen using pre-clinical analysis that identified them as likely to respond to ivacaftor. The list of residual function mutations eligible for inclusion in the trial are 2789+5G->A, D110E, R352Q, 3849+10kbC->T, D110H, A455E, 3272-26A->G, R117C, D579G, R1070W, 711+3A->G, E193K, S945L, F1074L, E56K, L206W, S977F, D1152H, P67L, F1052V, D1270N, R74W, R347H, K1060T, E831X.

 It should be noted that there are no pre-existing drug therapies presently available for those with one F508del gene alteration and one residual function alteration. 

The Cystic Fibrosis Foundation in the United States believes these triple combinations will allow us to eventually increase the number benefiting from these modulator therapies to over 90 percent of people with CF.