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.

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.

In February 2013, Vertex began two six-month, international Phase 3 clinical trials of Kalydeco and VX-809 in people with two copies of the Delta F508 mutation ages 12 and older. The studies will enroll approximately 1,000 volunteers at about 200 clinical trial sites in North America, Europe and Australia.

The U.S. Food and Drug Administration (FDA) has awarded Kalydeco and VX-809 “Breakthrough Therapy Designation,” which is intended to speed the development of select potential therapies that treat life-threatening diseases or conditions. As a result of this designation, the timeframe of the Phase 3 trials of Kalydeco and VX-809 has been considerably shortened to accelerate testing. Most Phase 3 trials are about one year long.

Vertex expects to submit a new drug application (NDA) to the FDA in 2014 for approval of the combination treatment for people with two copies of the Delta F508 mutation. About 50 percent of people with CF in the United States have two copies of the Delta F508 gene mutation.

How It Works

Results from an earlier 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 the defective protein to the cell surface; Kalydeco is designed to improve the protein’s function once it has reached the cell surface.

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 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.


What is the purpose of the Kalydeco™ and VX-809 Phase 3 clinical trial?

In February 2013, Vertex Pharmaceuticals began two international Phase 3 clinical trials of Kalydeco and VX-809 in combination.

The six-month studies will examine the combination treatment in people with two copies of the Delta F508 mutation ages 12 and older. Phase 3 trials are designed to collect data that the U.S. Food and Drug Administration (FDA) can use to decide whether to approve a potential drug.

The FDA has awarded Kalydeco and VX-809 “Breakthrough Therapy Designation,” which is intended to speed the development of select potential therapies that treat life-threatening diseases or conditions. As a result of this designation, the timeframe of the Phase 3 trials of Kalydeco and VX-809 has been considerably shortened to accelerate testing. Most Phase 3 trials are about one year long.

The studies will be conducted at approximately 200 clinical trial sites in North America, Europe and Australia and enroll a total of about 1,000 study volunteers. Each study will evaluate different doses of VX-809 in combination with Kalydeco.

In addition to the Phase 3 trials in those ages 12 and older, Vertex will conduct a six-month study of the combination treatment in children ages 6 to 11 with two copies of the Delta F508 mutation. Vertex will also conduct an eight-week, exploratory Phase 2 study of Kalydeco and VX-809 in people with one copy of the Delta F508 mutation.

Vertex plans to submit a new drug application (NDA) to the FDA in 2014 for approval of the combination treatment for people with two copies of the Delta F508 mutation.

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How can I learn more about enrolling in a Phase 3 combination trial?

For more information on the Phase 3 Kalydeco and VX-809 combination trials, speak with your CF doctor or call Vertex Medical Information at 1-877-634-8789.

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What is the difference between Kalydeco and VX-809?

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.

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 were the results of the Kalydeco and VX-809 Phase 2 clinical trial?

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.

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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?

It is too early to know. Vertex is conducting an eight-week, exploratory Phase 2 study of Kalydeco and VX-809 in people with one copy of the Delta F508 mutation.

In an earlier 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.

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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.

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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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 3/1/2013