Vertex Pharmaceuticals is developing two oral compounds designed to treat the basic defect in cystic fibrosis—a faulty gene and its protein product, called CFTR.
VX-770, the most advanced of the two compounds, is known as a potentiator and is designed to allow CFTR located at the cell surface to function correctly. In 2008, the CF Foundation and Vertex announced positive Phase 2 clinical trial results for patients who have the G551D gene mutation of CF.
VX-770 is currently being evaluated in a Phase 3 registration program that is comprised of three different clinical trials. The registration program is designed to generate data that the U.S. Food and Drug Administration can use to determine if VX-770 is safe, effective and acceptable for approval.
Vertex is also developing VX-809, known as a corrector, which is designed to move defective CFTR to its proper place in the cell.
VX-770 is currently being evaluated in a Phase 2a clinical trial.
What were the results of the Phase 2 study of VX-770?
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 39 cystic fibrosis patients over a 14-day or 28-day period. Additional trials are needed, but the early results are encouraging.
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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 measures of cystic fibrosis. 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 VX-770 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).
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Who is eligible to enroll in the Phase 3 clinical trials of VX-770?
Vertex initiated a Phase 3 registration program in May 2009. This program, if successful, is designed to meet FDA requirements for potential approval of VX-770.
The registration program is comprised of three different clinical trials. The first is a 48-week trial for patients age 12 years and older who carry a G551D mutation of CF. The second is a 48-week trial for patients ages 6 to 11 years who carry a G551D mutation of CF. The third trial is a 16-week study to evaluate for the first time patients age 12 years and older who are homozygous for the Delta F508 mutation of CF, the most common mutation in CF patients. Additional criteria for enrollment in these trials will be posted on www.clinicaltrials.gov.
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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.
back to topWhat patient population was VX-770 studied in during the Phase 2 trials?
VX-770 was studied in adults with the G551D mutation of CF in the Phase 2 trial.
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Why was the G551D mutation selected for the VX-770 clinical trial?
The G551D mutation was selected because the protein resulting from this mutation is located at the cell’s surface, waiting to function as a chloride channel, but does not function properly. VX-770 acts to increase the function of the CFTR chloride channel that is already at the cell surface.
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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. The Phase 3 registration program for VX-770 is testing the compound in patients with the G551D mutation of CF as well as patients who are homozygous for the Delta F508 mutation of CF.
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Why wasn’t the Delta F508 mutation chosen for the Phase 2 VX-770 clinical trials?
Because G551D is already located at the cell surface, these patients have the greatest potential to benefit from treatment with VX-770. Most Delta F508 protein is not at the cell surface and therefore it is unclear whether the patients with this mutation will benefit. The Phase 3 registration program of VX-770 will help determine if it is effective in this patient population.
It is possible that Delta F508 patients may need to have the location of their CFTR protein corrected to achieve the most benefit from VX-770. Vertex is developing another compound, VX-809, which is currently being studied in patients homozygous for the Delta F508 mutation. VX-809 is designed to increase the concentration of CFTR proteins at the cell surface.
back to topWhat 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 Phase 2 results showed that VX-770 improved lung function over 14 or 28 day period. Vertex is now initiating additional studies to examine VX-770 in a larger patient population and for a longer period of time.
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Will VX-770 or VX-809 benefit lung transplant patients?
We do not know yet if VX-770 or VX-809 will benefit transplant patients. Additional studies of the drug would be required.
back to topHow 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 trials. VX-770 is more advanced in clinical development and entered registration trials in May 2009. VX-809 is in Phase 2a clinical development. VX-770 is known as a potentiator, meaning that it opens the CFTR chloride channel. VX-809 is known as a corrector. We believe 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?
Vertex initiated Phase 3 registration program of VX-770 in May 2009. The registration program is comprised of three different clinical trials. The first is a 48-week trial for patients age 12 years and older who carry a G551D mutation of CF. The second is a 48-week trial for patients ages 6 to 11 years who carry a G551D mutation of CF. The third trial is a 16-week study to evaluate for the first time patients age 12 years and older who are homozygous for the Delta F508 mutation of CF, the most common mutation in CF patients. Additional criteria for enrollment in these trials will be posted on www.clinicaltrials.gov.
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What is the clinical trial timeline for VX-809?
In March 2009, Vertex initiated a Phase 2a clinical trial of VX-809 in patients homozygous for the Delta F508 mutation of CF.
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Are more patients needed for the next phase of clinical trials for these compounds?
Yes. Several hundred patients will be needed for upcoming trials of VX-770 and VX-809, including patients with the G551D mutation as well as patients with Delta F508 mutationl. Talk with your cystic fibrosis doctor for more information about these trials.
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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 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 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 reviewed by the Food and Drug Administration (FDA) and it must also 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.
Anyone participating in a clinical trial must sign an Informed Consent Form before they begin participating in a trial. This form explains the trial in full, including the risks and what is expected of a person if they take part in the trial. 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 6/12/09
