A Vertex triple-combination treatment for cystic fibrosis hit the mark in two Phase III trials, setting the stage for the company to secure approval for another treatment for the life-shortening genetic disease that affects approximately 75,000 people in North America, Europe and Australia.
This morning, Boston-based Vertex said its triple-combination treatment VX-445, tezacaftor and ivacaftor resulted in statistically significant improvements in lung function in two late-stage cystic fibrosis trials. The company said that data from a pre-specified interim analysis of the Phase 3 study in people with one F508del mutation and one minimal function mutation showed a mean absolute improvement in percent predicted forced expiratory volume in one second (ppFEV1). The improvement was 13.8 percentage points from baseline at week four of treatment compared to placebo, Vertex said.
In the Phase III study of people with two F508del mutations, the addition of VX-445 in patients already receiving tezacaftor and ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10 percentage points from baseline at week 4 of treatment compared to the control group in whom placebo was added to tezacaftor and ivacaftor.
Vertex said the combination treatment was generally well-tolerated by CF patients in the trial. The safety and efficacy data support the potential submission of a New Drug Application (NDA) for the VX-445 triple combination regimen, Vertex said.
Cystic fibrosis is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. The absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.
The results from the two trials announced this morning follows data Vertex announced late last year for another triple combination treatment, VX-659 and tezacaftor and ivacaftor. That trial data also showed a safety and efficacy profile supportive of a potential NDA submission, the company said. Because of the similarity of the four-week primary efficacy endpoint between the VX-659 and VX-445 regimens, as well as the near-term availability of the final 24-week data for both regimens in the second quarter of 2019, Vertex said it will use the data to select the best regimen to submit for regulatory approval. Because these submissions will include the final 24-week data, Vertex will seek approval for patients ages 12 and older with one F508delmutation and one minimal function mutation and for patients with two F508del mutations concurrently. The company plans to make its submission to the U.S. Food and Drug Administration, as well as other regulatory agencies, by the end of the fourth quarter.
“Both the VX-659 and VX-445 triple combination regimens showed highly consistent and significant improvements in lung function across our Phase 3 programs, underscoring the important clinical benefit that a triple combination regimen may provide to patients with two F508del mutations and to those with one F508del and one minimal function mutation,” Reshma Kewalramani, Vertex’s chief medical officer said in a statement. “We look forward to submitting global regulatory applications for one of these triple combination regimens for both patient populations later this year.”
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