-13.17 mmol/L reduction in sweat chloride in one arm supports further evaluation of a combination approach to treating the root cause of cystic fibrosis-
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
"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
About the Phase 2 Study
The results announced today are from Part 1 of a multiple-part, randomized, double-blind, placebo-controlled Phase 2 trial that will inform future clinical studies that combine a CFTR potentiator and corrector. The first part of the study enrolled 62 people with CF aged 18 years or older who had two copies of the F508del mutation in the CFTR gene. The primary goals of the trial were to evaluate the safety and tolerability and the effect on CFTR function of the combination of VX-770 and VX-809 as measured by sweat chloride.
There were three treatment arms in Part 1 of the study that evaluated VX-809 (200 mg) or placebo alone for 14 days, followed by VX-809 (200 mg) in combination with VX-770 (150 mg or 250 mg) or placebo for seven days.
Sweat Chloride: A co-primary endpoint of the study was the effect on CFTR function as measured by sweat chloride during the combination-dosing portion of the study (Day 14 to Day 21). Elevated sweat chloride levels are a diagnostic hallmark that occur in all people with CF and result directly from defective CFTR activity in epithelial cells in the sweat duct. The amount of chloride in the sweat is measured using a standard test. People with CF typically have elevated sweat chloride levels in excess of 60 mmol/L, while values in people who do not have CF are less than 40 mmol/L. Reduction in sweat chloride is considered to be a marker of improved CFTR function.
Within-Group Mean Change in Sweat Chloride From Baselines
Day 0 — 14:
Day 14 — 21: VX-809 in
Arm 1 (n=20): VX-809 (200mg);
-4.21 mmol/L (p=0.008)
|-2.24 mmol/L (p=0.163)|
Arm 2 (n=21): VX-809 (200mg);
|-9.10 mmol/L (p<0.001)|
Arm 3 (n=21): VX-809 placebo;
|-2.86 mmol/L (p=0.179)||+1.25 mmol/L (p=0.446)|
A statistically significant reduction in sweat chloride of -9.10 mmol/L (p<0.001) was observed after VX-770 (250 mg) was added to VX-809 (200 mg) from Day 14 to Day 21. As compared to baseline (Day 0), people who received the combination regimen in this arm had a -13.17 mmol/L reduction in sweat chloride.
Eight of the 17 patients with evaluable data in Arm 2 had a reduction of sweat chloride that exceeded -15.0 mmol/L, while four of these 17 patients had a reduction of sweat chloride that exceeded -20.0 mmol/L. Four of the 21 patients in this arm did not have evaluable data in this arm and were not part of this responder analysis (n=17). Across the treatment arms, patients returned to baseline following the completion of dosing with VX-809 and VX-770.
Vertex intends to initiate the second part of this Phase 2 study in the fourth quarter of 2011 following the conclusion of additional analyses of data from the first part of the study. Similar to Part 1, the second part of the study will evaluate multiple doses of VX-770 and VX-809 in combination and will focus on the effect of the combination on sweat chloride measurements. Part 2 of the study is also expected to evaluate longer dosing periods for the VX-770 and VX-809 combinations.
About CFTR and CFTR Modulators
CF is caused by defective or missing CF transmembrane conductance regulator (CFTR) proteins, which result in poor ion flow across cell membranes, including in the lungs, causing the accumulation of abnormally thick, sticky mucus that leads to chronic lung infections and progressive lung damage. In people with the F508del mutation, which is the most common CFTR mutation, CFTR proteins do not reach the cell surface in normal amounts. As a CFTR corrector, VX-809 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. Once these CFTR proteins are at the cell surface, VX-770, a CFTR potentiator, aims to further increase the function of the proteins by increasing their ability to transport ions across the cell membrane.
About Cystic Fibrosis
CF is a life-threatening genetic disease affecting approximately 30,000
Collaborative History with
Vertex initiated its CF research program in 1998 as a part of a
collaboration with CFFT, the non-profit drug discovery and development
affiliate of the
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
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Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements including
statements regarding (i) the interim data from Part 1 of the clinical
trial supporting further evaluation of a combination approach to
treating the root cause of cystic fibrosis; (ii) the intention to
initiate the second part of the clinical trial in the fourth quarter of
2011 after the completion of further analyses of data from Part 1; (iii)
the possibility of treating people with the most common form of CF by
using two medicines together that target the defective protein that
causes the disease; (iv) the hypothesis that enhanced CFTR function may
result in meaningful clinical benefits for people with CF; (v) Vertex's
expectations regarding the design of Part 2 of the clinical trial; and
(vi) VX-809 aiming to increase CFTR function by increasing the movement
of CFTR to the cell surface. While the Company believes the
forward-looking statements contained in this press release are accurate,
those statements are subject to risks and uncertainties that could cause
actual outcomes to vary materially from the outcomes referenced in the
forward-looking statements. These risks and uncertainties include, among
other things, the risk that efforts to develop VX-809 in combination
with VX-770 may not proceed due to technical, scientific, commercial,
financial or other reasons, that clinical trials may not proceed as
planned, that additional clinical trials involving VX-809 may not
generate data indicating that VX-809 is a useful treatment for cystic
fibrosis, that an adverse event profile for VX-809 or VX-770 could be
revealed in further nonclinical or clinical studies that could put
further development of VX-809 or VX-770 in jeopardy or adversely impact
the therapeutic value of VX-809 and/or VX-770, and other risks listed
under Risk Factors in Vertex's annual report and quarterly reports filed
(VRTX - GEN)
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