Medical News Briefs
Clinical Trials of Kalydeco in Combination with Other Potential CF Drugs Advance
Vertex Pharmaceuticals Inc. has launched clinical trials to test Kalydeco™ in combination with other potential therapies to treat the underlying cause of CF.
Vertex recently began two international Phase 3 clinical trials of Kalydeco combined with VX-809. The six-month studies will examine the combination treatment in people ages 12 and older who have two copies of the Delta F508 mutation, the most common mutation of CF.
More than 1,000 volunteers are participating in the Phase 3 studies at approximately 200 clinical trial sites in North America, Europe and Australia. Each study will evaluate different doses of VX-809 in combination with Kalydeco. Results from the Phase 3 trials are expected in mid-2014.
The U.S. Food and Drug Administration (FDA) has awarded Kalydeco and VX-809 “Breakthrough Therapy Designation,” which is intended to speed development of select potential therapies that treat life-threatening diseases or conditions. As a result, the timeframe of the Phase 3 trials for the combination treatment will be about half of what is typically required.
Phase 2 Study of Kalydeco and VX-661 Shows Promising Results
Vertex is also studying Kalydeco in combination with another potential CF therapy, VX-661. In April, the company announced promising results from a Phase 2 trial of the two drugs in combination in people with two copies of the Delta F508 mutation, ages 18 and older.
Study volunteers who received the Kalydeco and VX-661 combination treatment showed a significant improvement in lung function, compared with those who received a placebo. Four different doses of VX-661 were evaluated in combination with Kalydeco. People who received the two highest doses showed the greatest improvement in lung function.
Vertex plans to conduct more studies of Kalydeco and VX-661, pending discussion with regulatory agencies.
Like Kalydeco and VX-809, VX-661 is designed to treat the underlying cause of CF — a faulty gene and its protein product, CFTR. In January 2012, the FDA approved Kalydeco when taken alone for people with the G551D mutation of CF ages 6 and older. Kalydeco is now being studied when taken alone in patient groups that were not evaluated in earlier studies, including children as young as age 2 who have the G551D mutation.
In September, Vertex submitted a new drug application to the FDA for the approval of Kalydeco as a single therapy in people who have what are known as gating mutations of CF besides G551D. Results from a Phase 3 clinical trial of Kalydeco in people with these mutations showed that those who took the drug demonstrated improvements in lung function and weight gain, compared with study participants who received a placebo.
G551D is the most common gating mutation, found in about 4 percent of people with CF in the United States. The remaining gating mutations are found in about 1 percent of those living with the disease.
Research Programs to Treat Rare CF Mutations Move Forward
To help advance lifesaving drugs targeting the underlying cause of CF in all people with the disease, the Cystic Fibrosis Foundation is pursuing opportunities to find therapies to treat those with rare CF mutations, focusing on research to find drugs to treat “nonsense mutations,” which interrupt the production of a full-length CFTR protein. About 10 percent of people with CF have nonsense mutations,
One program, a collaboration between the CF Foundation Therapeutics (CFFT) laboratory in Boston and researchers at the University of Alabama at Birmingham, will screen drugs that have already been approved by the FDA to determine whether they can “read through,” or go past, the nonsense mutations and allow the production of a full-length CFTR protein.
Researchers will then evaluate promising compounds for CFTR activity in human airway cells containing nonsense mutations of CF. Because these compounds have already been approved by the FDA as safe for humans, if any appear to be effective in lab tests, they could potentially move more quickly into clinical studies in people with nonsense mutations.
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