Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from the first part of a Phase 2 study designed to evaluate multiple combination regimens of VX-770 and VX-809, Vertex's lead medicines in development that aim to treat the defective protein that causes cystic fibrosis (CF). That protein, known as the cystic fibrosis transmembrane conductance regulator (CFTR), is responsible for regulating the flow of chloride across the cell surface to help hydrate and clear mucus from the airways. The first part of the study enrolled and randomized 62 people with two copies of the most common mutation in the CF gene, known as the F508del mutation. In people with the F508del mutation, the CFTR protein does not reach the cell surface in normal amounts, resulting in a buildup of mucus and other complications that can lead to lung damage. VX-809, known as a CFTR corrector, is designed to help the protein reach the cell surface, while VX-770, known as a CFTR potentiator, aims to help the protein function more normally once it reaches the cell surface. VX-770 and VX-809 were advanced into development with support from Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit affiliate of the Cystic Fibrosis Foundation. Vertex retains worldwide rights to develop and commercialize these potential medicines.
The first part of the study met its two primary endpoints: (1) safety and tolerability of the combination regimen and (2) the effect of the combination of VX-770 and VX-809 on CFTR function as measured by sweat chloride, a key measure of the function of the CFTR protein. There were no serious adverse events reported, and the adverse event profile during the combination-dosing portion of the study (Day 14 to Day 21) was similar to that during the VX-809 monotherapy-dosing portion (Day 0 to 14). In the arm that evaluated VX-809 (200 mg) followed by dosing of VX-770 (250 mg) in combination with VX-809, a statistically significant reduction in sweat chloride of -13.17 mmol/L (p<0.001) was observed from baseline (Day 0) through Day 21. In this arm, a -9.10 mmol/L (p<0.001) reduction was observed after VX-770 (250 mg) was added to VX-809 (200 mg) for seven days (Day 14 to 21). Vertex intends to initiate the second part of this study in the fourth quarter of 2011 after the completion of further analyses of data from Part 1.
The most commonly reported adverse events were respiratory in nature and occurred in approximately half of people across all arms of the study. One person receiving VX-809 in the monotherapy portion of the study discontinued treatment due to an increase in respiratory symptoms during the first 7 days of the study.
"These data open the door to the possibility of treating people with the most common form of cystic fibrosis by using two medicines together that target the defective protein that causes the disease," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "We look forward to beginning the second part of this study later this year, which may help us begin to further explore the hypothesis that enhanced CFTR function may result in meaningful clinical benefits for people with cystic fibrosis."
"The CF Foundation's mission is to support the development of new medicines for cystic fibrosis that improve the quality of life for those with the disease," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "These data, while early, provide important new information about the potential to address the basic defect found among people with the most common form of CF."
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