Vertex commences VX-770 and VX-809 combination Phase 2a clinical trial for cystic fibrosis

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the initiation of a Phase 2a clinical trial that will evaluate multiple combinations of VX-770 and VX-809, investigational oral cystic fibrosis transmembrane conductance regulator (CFTR) modulators for the treatment of cystic fibrosis (CF). The trial is designed to evaluate the safety and tolerability of VX-809 dosed alone for 14 days followed by dosing of VX-809 in combination with VX-770 for 7 days. The trial will also assess the effect of VX-809 alone and in combination with VX-770 on CFTR function, as measured by sweat chloride. The three-part trial is designed to enroll up to a total of 160 people with two copies of the F508del CFTR mutation, the most common mutation in the CFTR gene.

“This is the first opportunity to evaluate the use of two CFTR modulator compounds with potentially complementary mechanisms and may provide important insight into the role these types of compounds may play in the future treatment of people with CF.”

CF is caused by defective or missing CFTR proteins, which result in poor ion flow across cell membranes, including in the lung, and the accumulation of abnormally thick, sticky mucus that leads to chronic lung infections and progressive lung damage. VX-770, known as a CFTR potentiator, aims to increase the function of defective CFTR proteins by increasing the gating activity, or ability to transport ions across the cell membrane, of CFTR at the cell surface. In people with the F508del mutation, CFTR proteins do not reach the cell surface in normal amounts. VX-809, known as a CFTR corrector, aims to increase CFTR function by increasing the trafficking, or movement, of CFTR to the cell surface. The trial announced today will be the first to evaluate whether a combination regimen of VX-770 and VX-809 can improve CFTR function by increasing both the gating and trafficking of CFTR in people with CF.

"The start of this trial has been greatly anticipated by the CF community and marks a milestone in our efforts to discover and develop new treatments to address the underlying cause of this disease," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "This is the first opportunity to evaluate the use of two CFTR modulator compounds with potentially complementary mechanisms and may provide important insight into the role these types of compounds may play in the future treatment of people with CF."

"Our approach to the treatment of CF underscores Vertex's commitment to innovative science that seeks to better understand and fundamentally change the way life-threatening diseases are treated," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Importantly, this trial will inform the development path for future studies combining novel CFTR modulators for the treatment of people with the most common mutation of CF, known as F508del."

VX-770 and VX-809 were discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) to discover and develop novel CFTR modulators. CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex retains worldwide rights to develop and commercialize VX-770 and VX-809.