Vertex Reports Positive, Interim Late-Stage Results from Triple Combo Therapy for CF

Rare Daily Staff

Vertex Pharmaceuticals said that treatment with a triple combination of its next-generation corrector VX-659, tezacaftor, and ivacaftor resulted in statistically significant improvements in lung function in two late-stage studies in people with cystic fibrosis (CF).

CF is a rare, life-shortening genetic disease caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or 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.

Vertex already markets the combination of its CF drugs tezacaftor and ivacaftor under the brand name Symdeko.

Data from a pre-specified interim analysis of a phase 3 randomized study of 111 people ages 12 or older with one F508del mutation and one minimal function mutation showed a statistically significant improvements in lung function as measured by ppFEV₁ (percent predicted forced expiratory volume in one second). The study showed a mean absolute improvement in ppFEV₁ of 14.0 percentage points from baseline at week 4 of treatment compared to placebo.

In the phase 3 study in people with two F508del mutations, the addition of VX-659 in patients already receiving tezacaftor and ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10.0 percentage points from baseline at week 4 of treatment compared to the control group in whom placebo was added to tezacaftor and ivacaftor. This study is ongoing to evaluate the VX-659 triple combination regimen for a total of 24 weeks and will generate additional safety and efficacy data and data for key secondary endpoints

The company said VX-659 triple combination regimen was generally well tolerated, and the safety and efficacy profile from the results released today supports the potential submission of an application to regulators for marketing approval for the VX-659 triple combination regimen.

Vertex also announced that enrollment is complete for the two phase 3 studies of the triple combination of the next-generation corrector VX-445, tezacaftor, and ivacaftor in people with CF with one F508del mutation and one minimal function mutation and in people with two F508del mutations. Vertex remains on track to report topline data from both phase 3 studies of the VX-445 triple combination regimen in the first quarter of 2019.

“These data mark a major milestone in our efforts to develop new CF medicines as they underscore the important clinical benefit that a triple combination regimen may provide to the vast majority of CF patients who have at least one F508del mutation,” said Reshma Kewalramani, executive vice president of global medicines development and medical affairs and chief medical officer of Vertex. “We plan to evaluate data for the VX-445 and VX-659 triple combination regimens in the first quarter of next year and to choose the best regimen to submit for potential approval with the goal of bringing forward a new treatment option to those with one F508del mutation and one minimal function mutation and to those with two F508del mutations as rapidly as possible.”

Data from studies of VX-659 and VX-445 will also be used for regulatory submissions outside of the United States planned for late 2019.

November 28, 2018
Photo: Reshma Kewalramani, executive vice president of global medicines development and medical affairs and chief medical officer of Vertex