On March 27, 2008, the Cystic Fibrosis Foundation announced that VX-770, an oral drug in development that targets a basic defect in cystic fibrosis, showed promising results in an ongoing Phase 2a clinical trial for patients who carry the G551D gene mutation of CF. The drug is being developed by Vertex Pharmaceuticals Incorporated.
What are the results of the study?
A Phase 2 clinical trial of the Vertex compound VX-770 showed that the compound, when taken orally, improved several key indicators of cystic fibrosis, including lung function, nasal potential difference measures and sweat chloride levels.
This suggests that VX-770 acts to improve function of the malformed CFTR protein. This was a small, short-term study with 20 cystic fibrosis patients over a 14-day period. Additional studies are needed, but the early results are very promising.
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Why is this important?
These findings are significant because, for the first time, we know that a chemical compound has the ability to affect several key cystic fibrosis measures. All the therapies currently on the market for CF address the symptoms of the disease, but it now appears that we can improve key CF measures by targeting the basic defect: the faulty CFTR protein.
We have achieved what is known in the scientific world as "proof of concept." Our "concept" was that we can improve key measures of CF by restoring the function of the defective CFTR protein. This study is a big step toward proving that concept. These findings could have important implications for other studies and drugs in development.
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What is the timeline for getting this compound into patients' hands?
It is too early to speculate on this. It takes several years for a promising drug to make it from 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 Food and Drug Administration (FDA). We are planning these necessary studies and they will take place over the next few years.
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Is VX-770 a pill?
Yes. VX-770 is a pill that is taken orally. It is not an inhaled therapy.
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What patient population was VX-770 studied in?
VX-770 was studied in adults with the G551D mutation of CF. Further clinical trials are necessary for us to learn more about the total number of patients who might benefit from this therapy.
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Why was the G551D mutation selected for the VX-770 clinical trial?
The G551D mutation was the ideal mutation to start with because the protein from this mutation is located at the cell’s surface, waiting to function as a chloride channel. VX-770 acts to create a more effective opening of the CFTR chloride channel already at the cell surface. This makes the G551D mutation an obvious choice for studying VX-770.
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Will VX-770 work for patients with other mutations of cystic fibrosis?
We don’t know for sure. More studies are necessary to determine what other CF mutations may benefit from VX-770.
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Why wasn’t the DF508 mutation chosen for the VX-770 clinical trial?
Because G551D is at the cell’s surface, it is the obvious choice to study VX-770. Most DF508 protein is not at the cell surface and therefore it is unclear whether the patients with this mutation will benefit, but it is possible. These patients may need to have the location of their CFTR protein corrected to achieve the most benefit from VX-770.
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What percentage of the CF population has the G551D mutation?
Three to four percent of the cystic fibrosis patient population has the G551D mutation.
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What does this mean for CF patients with the G551D mutation?
The preliminary results show that VX-770 could improve lung function. More studies are necessary, however.
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Will VX-770 benefit lung transplant patients?
We do not know yet if VX-770 will benefit transplant patients. Additional studies of the drug would be required.
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How does this work relate to the other Vertex compound, VX-809?
VX-770 and VX-809 are two individual compounds being evaluated in separate clinical studies. VX-770 is more advanced in clinical trials (Phase 2a), and VX-809 is still in Phase 1 studies (meaning it's being tested in healthy volunteers).
VX-770 is known as a "potentiator," meaning that it opens the CFTR chloride channel. VX-809 is known as a “corrector.” We think that VX-809 improves CFTR function by helping CFTR to arrive at the proper location on the cell surface.
Both of these compounds are being tested in separate clinical trials for their ability to restore CFTR function.
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What is the clinical trial timeline for VX-770?
The second part of the Phase 2a clinical trial is scheduled to begin in the second quarter of 2008. A Phase 2b clinical trial is planned to begin some time in 2009. There are no details now about a Phase 3 clinical trial.
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Are more patients needed for the next phase of clinical trials?
Yes.
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How can I participate?
Talk to your cystic fibrosis doctor or call (877) 8CF-JOIN. Or, click here to Find a Clinical Trial. Once there, enter the keyword "Vertex."
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How safe are clinical trials for cystic fibrosis?
Nothing is more important than safety in developing new cystic fibrosis treatments. There are four layers of protection in every clinical trial for cystic fibrosis. Each trial must be determined as safe and appropriate for patients by 1) the CF Foundation, 2) the FDA, 3) the participating hospital or university’s Institutional Review Board (IRB), and 4) the Data Safety Monitoring Board (DSMB). The DSMB is an independent committee of experts in cystic fibrosis 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 cystic fibrosis 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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