Vertex Pharmaceuticals Incorporated is developing two oral investigational drugs, VX-809 and VX-770, aimed at treating the basic defect in cystic fibrosis — a faulty gene and its protein product, called CFTR.
Through its Therapeutics Development Program, the CF Foundation collaborated with Vertex to discover and develop VX-809 and VX-770, investing approximately $76 million in the effort. This represents the largest single investment in CF drug discovery by the Foundation.
VX-770 is designed to allow CFTR located at the cell surface to function correctly.
VX-770 is currently in Phase 3 clinical trials and is being studied in patients who have the G551D gene mutation of CF.
VX-809 is designed to move defective CFTR to its proper place at the cell surface. VX-809 recently completed a Phase 2a trial in patients with the Delta F508 mutation, the most common mutation in CF.
Vertex Pharmaceuticals announced results from the Phase 2a trial of VX-809 on February 3, 2010.
What was the purpose of the VX-809 Phase 2a study?
The Phase 2a trial of VX-809 examined the safety and efficacy of the therapy over a 28-day period. The primary focus of the study was safety and tolerability, but researchers also looked to see if VX-809 improved key indicators of cystic fibrosis, including sweat chloride levels.
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What were the results of the Phase 2a study of VX-809?
VX-809 was found to be well-tolerated. In a subset of patients, the therapy also reduced sweat chloride levels — a key indicator of CF. A reduction in sweat chloride levels suggests that VX-809 may improve the function of CFTR, the faulty protein in CF.
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What patient population was VX-809 studied in?
VX-809 was studied in CF patients who have two copies of the Delta F508 mutation of CF. The Delta F508 mutation leads to a CFTR protein that is not folded correctly. Because CFTR is not the right shape, it does not make it to the surface of the cell. VX-809 is designed to allow the protein to fold correctly so it can move to its proper place at the cell surface.
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What is the next step for VX-809?
Using a single drug to correct a misfolded protein — like the CFTR protein in the Delta F508 mutation of CF — is very challenging.
Research in the laboratory suggests that using two therapies in combination may increase CFTR function in cells with the Delta F508 mutation when compared to using a single therapy alone.
VX-809 is designed to move defective CFTR to its proper place at the cell surface. VX-770 is designed to allow CFTR located at the cell surface to function better. Some researchers believe that by using VX-809 in combination with VX-770, CFTR function may be further increased in patients with CF.
The first trial examining VX-809 and VX-770 in combination in CF patients is currently in the planning phases, and is expected to begin in the United States in the second half of 2010.
In addition, Vertex is further reviewing the Phase 2a data and may explore the option of studying VX-809 as a single drug in higher doses in a separate clinical trial.
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What percentage of the CF population has the Delta F508 mutation?
Approximately 50 percent of people with CF in the United States have two copies of the Delta F508 gene mutation. Nearly 90 percent of people with CF in the United States have at least one copy of the Delta F508 mutation.
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How does VX-809 relate to Vertex’s other compound, VX-770?
VX-809 and VX-770 are two individual compounds being evaluated in separate clinical trials. VX-770 is further along in clinical development and entered Phase 3 registration trials in May 2009. VX-809 just completed a Phase 2a clinical trial.
The first trial examining VX-809 and VX-770 in combination in CF patients is currently in the planning phases, and is expected to begin in the United States later this year.
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Are more patients needed for the next phase of clinical trials for VX-809?
Yes, patients will be needed for the upcoming trials, however we are not currently enrolling patients. For more information, talk with your cystic fibrosis doctor or call (877) 8CF-JOIN.
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Will VX-809 work for patients with other mutations of cystic fibrosis?
VX-809 was studied in CF patients who have two copies of the Delta F508 mutation of CF. At this time we don’t know what other mutations may respond to VX-809. More studies would be necessary to determine what other CF mutations may benefit from VX-770.
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When will VX-809 be available?
It is too early to speculate on this. It takes several years for a promising drug to make it from clinical trials to the pharmacy shelf. We are going as fast as we can, but additional trials are necessary before we know whether this promising compound will be approved by the U.S. Food and Drug Administration (FDA).
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How safe are CF clinical trials?Nothing is more important than safety in developing new CF treatments. There are four layers of protection in every CF clinical trial. Each trial must be determined as safe and appropriate for patients by the:
- CF Foundation;
- FDA;
- Participating hospital or university’s Institutional Review Board (IRB); and
- Data Safety Monitoring Board (DSMB). The DSMB is an independent committee of experts in CF care that checks information on ongoing trials, watching for possible problems or unwanted side effects.
The CF Foundation is the only voluntary health organization to organize a DSMB whose members are experts in CF and completely independent and not involved in any way with the trial or its participants. In this way, the CF Foundation does its best to keep participants safe throughout the clinical trial.
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How is my safety protected broadly?
The U.S. government has strict guidelines and safeguards to help protect people who choose to participate in clinical research. Every clinical trial in the United States must be approved and monitored by an IRB. This is to keep risks as low as possible and ensure that the risks are worth any potential benefits.
The IRB is usually made up of doctors and the general public. They look at the trial’s protocol (a clear and detailed plan of the experiment) to make sure that participants’ rights are protected and the trial does not cause them unnecessary risk.
The FDA also must approve all clinical trial protocols and make sure all of their procedures are being followed as the trial goes on.
In the United States, anyone participating in a clinical trial must sign an Informed Consent Form. This form explains the trial in full, including the risks, and a research team member will explain the trial and the consent form to individuals before they sign it.
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Where can I find more information about clinical trials in general?
To learn more about cystic fibrosis clinical trials, click here.
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Updated 02/03/10
