One week after Vertex Pharmaceuticals Incorporated initiated its first Phase 3 study of VX-659, tezacaftor and ivacaftor regimen for people with cystic fibrosis, the company has announced it is initiating a second.
One week after Vertex Pharmaceuticals Incorporated initiated its first Phase 3 study of VX-659, tezacaftor and ivacaftor regimen for people with cystic fibrosis (CF), the company has announced it is initiating a second.
Last week’s announcement came on the heels of Vertex initiating the investigational triple combination for 360 people with CF who have one F508del mutation and one minimal function mutation. The latest study to be initiated intends to enroll 100 patients with two copies of the F508del mutation. Two copies of the F508del mutation is the most common genetic variation of CF.
The study’s primary endpoint is the mean absolute change from baseline in percent predicted forced expiratory volume in one second (ppFEV1) at week four of treatment.
“The first Phase 3 study we announced in February is designed to support approval of the VX-659 triple combination in patients with one F508del mutation and one minimal function mutation who currently have no treatment that addresses the underlying cause of disease,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “This second study is designed to enable us to broaden the potential label for this regimen to include those with the most common genetic form of cystic fibrosis.”
The 508del mutation typically results in reduced activity of conductance regulator (CFTR) protein and loss of chloride secretion. The combination can lead to impaction of mucus in the airways, gastrointestinal tract, and exocrine organs, and it can eventually result in stark clinical consequences, including continual loss of lung function, nutritional insufficiencies, pulmonary exacerbations, and respiratory failure.
The initiation of the Phase 3 study in this indication is based on data announced today from a Phase 2 study that exhibited a mean absolute improvement of ppFEV1 of 9.7 percentage points from baseline through week four of treatment when 400 mg of VX-659 was added to tezacaftor in combination with ivacaftor. In the study, the triple combination regimen was generally well tolerated, and the majority of adverse events (AEs) were mild to moderate in severity and there were no discontinuations due to AEs.
“We continue to make rapid and significant progress in our efforts to advance our two triple combination regimens into Phase 3 development, with an ultimate goal of bringing the best triple combination to patients as quickly as possible,” said Chodakewitz.
The study will evaluate a fixed-dose combination of VX-659 (240 mg) with tezacaftor (100 mg) and ivacaftor (150 mg) in the morning followed by ivacaftor (150 mg) in the evening, which is the same dosing regimen being evaluated in the ongoing Phase 3 study in patients with one F508del mutation and one minimal function mutation.
The Phase 3 is designed to support an application for U.S. Food and Drug Administration (FDA) approval of the triple combination regimen in patients with this variation of CF, and could potentially broaden the label should the therapy be approved. Data from the study in patients with two F508del mutations will be used to support planned regulatory submissions in Europe and other regions.
In addition to the work being done to evaluate VX-659 as part of a triple combination therapy for people with CF, Vertex also has plans to initiate a Phase 3 program to evaluate another gene corrector, VX-445, in combination with tezacaftor and VX-561.