FAQs About Combined Kalydeco™ & VX-809 Clinical Trial
Vertex Pharmaceuticals Inc. is studying its cystic fibrosis drug Kalydeco™ in combination with another potential therapy, VX-809, in people with the most common mutation of CF, Delta F508.
Vertex Pharmaceuticals Inc. is studying its cystic fibrosis drug Kalydeco™ in combination with another potential therapy, VX-809, in people with the most common mutation of CF, Delta F508.
Both drugs are designed to treat the underlying cause of cystic fibrosis — a faulty gene and its protein product, CFTR — and are taken in pill form.
Results from a Phase 2 clinical trial of Kalydeco and VX-809 in multiple combinations showed significant improvements in lung function in people with two copies of the Delta F508 mutation.
The Delta F508 mutation creates a defective protein that does not move to its proper place at the cell surface. VX-809 is designed to move CFTR to the cell surface; Kalydeco is designed to improve the protein’s function once it has reached the cell surface.
Vertex plans to begin a pivotal trial of Kalydeco and VX-809 in people with two copies of the Delta F508 mutation in early 2013, pending discussion with regulatory agencies.
Vertex plans to begin a pivotal trial of Kalydeco and VX-809 in people with two copies of the Delta F508 mutation in early 2013, pending discussion with regulatory agencies.
The U.S. Food and Drug Administration (FDA) approved Kalydeco in January 2012 when taken alone for people with the G551D mutation of CF ages 6 and older.
Kalydeco was formerly called VX-770 and is also known by its generic name ivacaftor.
Vertex developed Kalydeco and VX-809 with significant scientific, clinical and financial support from the Cystic Fibrosis Foundation, including a $75 million investment.
Vertex developed Kalydeco and VX-809 with significant scientific, clinical and financial support from the Cystic Fibrosis Foundation, including a $75 million investment.
In June 2012, Vertex announced results from the second part of a Phase 2 clinical trial of Kalydeco and VX-809 in combination. The trial enrolled 109 people ages 18 and older with at least one copy of the Delta F508 mutation of CF.
People who received the combination treatment showed improvements in lung function, compared with those who received a placebo.
Those with two copies of the Delta F508 who received the highest dose of VX-809 had the greatest improvement. More than half of this group had an improvement in lung function of 5 percentage points, compared with those on placebo, and a quarter of this group had an improvement of 10 percentage points or more.
Participants with one copy of the Delta F508 mutation also showed improvements in lung function, however, the improvements were smaller than those seen in people with two copies of Delta F508.
The study also evaluated the safety and tolerability of the combination therapy. There were no serious adverse events reported during the trial.
back to topPeople who received the combination treatment showed improvements in lung function, compared with those who received a placebo.
Those with two copies of the Delta F508 who received the highest dose of VX-809 had the greatest improvement. More than half of this group had an improvement in lung function of 5 percentage points, compared with those on placebo, and a quarter of this group had an improvement of 10 percentage points or more.
Participants with one copy of the Delta F508 mutation also showed improvements in lung function, however, the improvements were smaller than those seen in people with two copies of Delta F508.
The study also evaluated the safety and tolerability of the combination therapy. There were no serious adverse events reported during the trial.
Kalydeco and VX-809 are two individual drugs that have been studied in separate clinical trials and are currently being studied in combination in people with the Delta F508 mutation of CF.
Kalydeco was approved by the FDA in January 2012 for people with the G551D mutation of CF ages 6 and older.
In people with the G551D mutation, Kalydeco helps improve the function of the defective CFTR protein at the surface of the cell. Kalydeco allows CFTR that is at the cell surface to function better, allowing a proper flow of salt and fluids on the surface of the lungs. This helps to thin the thick, sticky mucus caused by CF that builds up in the lungs.
In people with the G551D mutation, Kalydeco helps improve the function of the defective CFTR protein at the surface of the cell. Kalydeco allows CFTR that is at the cell surface to function better, allowing a proper flow of salt and fluids on the surface of the lungs. This helps to thin the thick, sticky mucus caused by CF that builds up in the lungs.
VX-809 is designed to move the defective CFTR protein to its proper place at the cell surface. The Delta F508 mutation leads to a CFTR protein that does not fold correctly. Because the defective CFTR is not the right shape, it does not make it to the surface of the cell.
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What are the next steps for the Kalydeco and VX-809 combination trial?
Vertex plans to begin a pivotal trial of the combination treatment in people with two copies of the Delta F508 mutation of CF in early 2013, pending discussion with regulatory agencies. Pivotal trials are usually Phase 3 trials, designed to collect data that the U.S. Food and Drug Administration can use to decide whether to approve a potential drug.
Vertex has also said it will conduct additional studies of Kalydeco and VX-809 in combination in people with one copy of the Delta F508 mutation.
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Vertex plans to begin a pivotal trial of the combination treatment in people with two copies of the Delta F508 mutation of CF in early 2013, pending discussion with regulatory agencies. Pivotal trials are usually Phase 3 trials, designed to collect data that the U.S. Food and Drug Administration can use to decide whether to approve a potential drug.
Vertex has also said it will conduct additional studies of Kalydeco and VX-809 in combination in people with one copy of the Delta F508 mutation.
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Will the Kalydeco and VX-809 combination therapy help people who have one copy of the Delta F508 mutation and a copy of another mutation?
In the Phase 2 trial of Kalydeco and VX-809 in combination, participants with one copy of the Delta F508 mutation showed improvements in lung function, compared with those on placebo. However, these improvements were smaller than those seen in people with two copies of Delta F508.
Vertex has said it will conduct additional studies of Kalydeco and VX-809 in combination in people with one copy of the Delta F508 mutation.
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In the Phase 2 trial of Kalydeco and VX-809 in combination, participants with one copy of the Delta F508 mutation showed improvements in lung function, compared with those on placebo. However, these improvements were smaller than those seen in people with two copies of Delta F508.
Vertex has said it will conduct additional studies of Kalydeco and VX-809 in combination in people with one copy of the Delta F508 mutation.
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How many people with CF have the Delta F508 mutation?
About 50 percent of people with CF in the United States have two copies of the Delta F508 gene mutation. About 40 percent of people with CF in the United States have at least one copy of the Delta F508 mutation.
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How can I find out which CF mutations I or my child have?
If you do not know what your or your child's two CF mutations are, contact your CF doctor or care center.
How can I find out which CF mutations I or my child have?
If you do not know what your or your child's two CF mutations are, contact your CF doctor or care center.
The Cystic Fibrosis Foundation’s Mutation Analysis Program (MAP) offers free and confidential genetic testing to patients with a confirmed diagnosis of cystic fibrosis. The MAP provides genotyping for cystic fibrosis patients who have not yet been tested, or who have been tested previously but still have one or more unknown mutations.
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 if I participate in a clinical trial?
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 institutional review board (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.
In addition, an independent committee of experts in CF care, the Data Safety Monitoring Board (DSMB), examines data from clinical trials and determines if there are safety issues that need to be brought to the attention of the IRB or the sponsors of a clinical trial.
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.
back to top
How is my safety protected broadly if I participate in a clinical trial?
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 institutional review board (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.
In addition, an independent committee of experts in CF care, the Data Safety Monitoring Board (DSMB), examines data from clinical trials and determines if there are safety issues that need to be brought to the attention of the IRB or the sponsors of a clinical trial.
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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