Vertex Pharmaceuticals is set to commence a Phase III development programme of the once-daily experimental combination of VX-121, tezacaftor and VX-561 (deutivacaftor) for cystic fibrosis.
Slated to begin in the second half of this year, the Phase III programme will involve two randomised, double-blind, active-controlled clinical trials.
These 48-week trials will analyse the safety and efficacy of the combination regimen of VX-121 20mg, tezacaftor 100mg and VX-561 250mg as against Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor).
The first trial will have nearly 350 CF patients aged 12 years or above with one F508del mutation and one minimal function mutation.
The second trial plans to enrol about 450 CF patients of the same age group with one or two F508del mutations and another mutation that responds to cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
The non-inferiority to Trikafta on the absolute change from baseline in per cent predicted forced expiratory volume in one second (ppFEV1) will be the primary goal for both trials.
In addition, the trials will evaluate absolute change from baseline in ppFEV1 and sweat chloride for superiority to Trikafta.
The plans to initiate the Phase III programme come after Vertex obtained positive data in a Phase II trial in CF patients aged 18 years and above.
The combination treatment was generally well-tolerated in the trial.
Furthermore, the trial met the primary efficacy goal of absolute change from baseline in ppFEV1 and all secondary efficacy goals.
Vertex noted that these results indicate that the regimen could potentially restore CFTR function in CF patients to increased levels and offer improved clinical benefit versus its other CFTR modulators such as Trikafta.
Vertex Pharmaceuticals chief medical officer and Global Medicines Development and Medical Affairs executive vice-president Carmen Bozic said: “With this once-daily, next-in-class, triple combination regimen, our goal is to develop a more effective treatment regimen with the potential to restore CFTR function in people with CF to even higher levels than currently achievable.”