Vertex Pharmaceuticals Inc. is studying its cystic fibrosis drug Kalydeco™ (formerly known as VX-770) 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.
The U.S. Food and Drug Administration (FDA) has approved Kalydeco (kuh-LYE-deh-koh) when taken alone for people with the G551D mutation of CF ages 6 and older. VX-809 is still in development. The two drugs are taken in pill form.
An ongoing Phase 2 clinical trial is testing the safety and tolerability of the two drugs in multiple combinations in people ages 18 and older with at least one copy 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. Researchers believe that a combination of VX-809 and Kalydeco may work better than using either drug alone in people with this mutation.
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 developed Kalydeco and VX-809 with significant scientific, clinical and financial support from the Cystic Fibrosis Foundation, including an approximately $75 million investment.
What is the status of the Kalydeco™ and VX-809 Phase 2 clinical trial?
The second part of the ongoing Phase 2 clinical trial of Kalydeco and VX-809 in combination is enrolling volunteers ages 18 and older with at least one copy of the Delta F508 mutation of CF.
The main goals of the Phase 2 trial are to measure the effect of the combination treatment on sweat chloride levels and evaluate its safety and tolerability. The two drugs will be studied over a longer period of time than in the first part of the study.
Results from the second part of the Phase 2 study are expected in mid-2012.
For more information about this trial, talk to your cystic fibrosis doctor, or call toll free 1-877-823-5646 (1-877-8CF-JOIN). Or, click here to find a clinical trial. Once there, select "Advanced Search," enter the keyword "Vertex" and click on "Get Results."
You can find additional information on enrollment in this clinical trial at www.clinicaltrials.gov.
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What is the purpose of evaluating Kalydeco and VX-809 as a combination therapy?
The Phase 2 clinical trial is testing the drugs in people ages 18 and older with the most common mutation of CF, Delta F508.
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.
Research in the laboratory suggests that, in people with the Delta F508 mutation, using more than one drug may work better on the defective CFTR protein than using one drug alone.
VX-809 is designed to move the defective CFTR protein to the cell surface. Kalydeco is designed to allow CFTR located 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.
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What were the results of the first part of the Phase 2 combination trial of Kalydeco and VX-809?
In June 2011, Vertex announced the results of the first part of the Phase 2 clinical trial of combinations of Kalydeco and VX-809. In this trial, 62 patients ages 18 and older with two copies of the Delta F508 mutation were enrolled in three groups.
Two groups received VX-809 for 14 days, followed by Kalydeco and VX-809 in combination for seven days. One of these groups received a higher dose of Kalydeco. The third group received a placebo throughout the trial.
Patients who received the drugs had a positive change in sweat chloride levels. Those in the group receiving the higher dose of Kalydeco in combination with VX-809 had a greater reduction in sweat chloride than those who took the smaller dose of Kalydeco.
The study also evaluated the safety and tolerability of the combination therapy. There were no serious adverse events reported during the trial.
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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. 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 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. To learn more about the MAP, talk with your CF doctor or care center.
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What is the difference between Kalydeco and VX-809?
Kalydeco and VX-809 are two individual drugs that have been evaluated in separate clinical trials and are currently being studied in combination.
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. The drug has shown it can markedly improve lung function, lower sweat chloride levels and help patients gain weight.
VX-809 is designed to move defective CFTR protein to its proper place at the cell surface. A Phase 2a clinical trial of the drug in patients with the most common mutation of CF, Delta F508, showed positive results.
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How can I enroll in the combination trial?
For more information about this trial, talk to your cystic fibrosis doctor, or call toll free 1-877-823-5646 (1-877-8CF-JOIN). Or, click here to find a clinical trial. Once there, select "Advanced Search," enter the keyword "Vertex" and click on "Get Results."
You can find additional information on enrollment in this clinical trial at www.clinicaltrials.gov.
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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 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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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 2/8/2012
