New Jersey biopharmaceutical company PTC Therapeutics recently declared its intention to do whatever it takes — including an additional clinical trial — to seek approval for ataluren (formerly PTC124) as a treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) caused by nonsense mutations in the gene for the muscle protein dystrophin.
Nonsense mutations — also known as premature stop codon mutations— cause cells to stop synthesizing a protein from genetic instructions before the process is complete, resulting in production of a short, nonfunctional protein.
These mutations are believed to be the underlying cause of DMD or BMD in about 10 to 15 percent of people with these dystrophies, both of which result from a lack of dystrophin in muscle cells.
Ataluren is designed to coax cells to ignore, or "read through," nonsense mutations and synthesize a functional dystrophin protein. The drug is sometimes referred to as a "stop codon read-through" compound.
MDA Venture Philanthropy, the drug development arm of MDA's translational research program, awarded $1.5 million to PTC in 2005 for ataluren research.
In a July 11, 2012, email communication to advocacy groups, PTC said that the U.S. Food and Drug Administration (FDA) will almost certainly require an additional clinical trial of ataluren in nonsense-mutation DMD/BMD comparing low-dose ataluren to a placebo.
A 48-week, 174-participant trial suggested a benefit for those on a lower dose of ataluren with respect to the distance walked in six minutes for participants with nonsense-mutation DMD/BMD while participants on high-dose ataluren or placebo showed no benefit. (Those on the low dose walked about 100 feet farther in six minutes than those in the high-dose or placebo groups, although all groups' walking distance declined during the trial.)
In the same July communication, PTC said that it is in discussions with the European Medicines Agency (EMA) concerning the path forward in Europe, particularly the potential to file for "conditional" approval of ataluren for DMD/BMD.
"Whether in the context of conditional approval in Europe, or to meet additional requirements in the US, PTC is currently planning to conduct an additional confirmatory study of low-dose ataluren versus placebo," the communication said.
Open-label trials of ataluren for those who have previously participated in placebo-controlled trials of the drug are currently being conducted in the United States and in several other countries.
Open-label studies are those in which all participants receive the experimental treatment. Placebo-controlled studies are those in which some participants receive a placebo (look-alike, inactive drug) and in which neither the investigators nor the participants know who is receiving which treatment until the study is complete.
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