A trial of the exon-skipping drug eteplirsen resulted in an increase in both dystrophin production and walking ability in boys with Duchenne MD
Update (Aug. 8, 2013): This story has been updated to reflect the Aug. 1, 2013, publication of these trial results in Annals of Neurology.
Editor's note (Oct. 3, 2012): Please read A Closer Look at the 48-Week Eteplirsen Trial Results for a more in-depth discussion of the phase 2b trial in boys with Duchenne MD.
The biopharmaceutical company Sarepta Therapeutics announced today that its experimental exon-skipping compound, eteplirsen, resulted in an increase in dystrophin and "significant clinical benefit" on the six-minute walk test in a phase 2b trial in boys with Duchenne muscular dystrophy (DMD) caused by specific mutations.
In an Oct. 3, 2012, press release, the company said that trial participants who received weekly intravenous infusions of eteplirsen for 48 weeks walked an average of 89.4 meters (293 feet) farther in six minutes than "placebo/delayed treatment" trial participants who received placebo infusions for the first 24 weeks and then eteplirsen for 24 weeks in the open-label extension study.
Participants who received 48 weeks of eteplirsen demonstrated an increase of 21 meters (about 69 feet) in distance walked compared to their baseline test, while those who received placebo/delayed treatment showed a decline of 68.4 meters (224.4 feet) compared to baseline.
Infusions of eteplirsen for 48 weeks resulted in a statistically significant increase in dystrophin-positive muscle fibers, to 47 percent of normal. The placebo/delayed treatment group also showed a statistically significant increase in dystrophin-positive muscle fibers, to 38.3 percent of normal, the company reported. A lack of the muscle protein dystrophin is the underlying cause of DMD.
No treatment-associated adverse events were reported.
Eteplirsen is designed to skip exon 51 of the dystrophin gene, and potentially could benefit about 13 percent of boys with DMD.
"These data represent a significant milestone and a defining moment of progress and hope for patients with DMD and their families, as well as for those of us in the scientific community who have been pursuing potential treatments for this devastating and deadly disease for decades," said Jerry Mendell, principal investigator of the study, and director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital.
"While eteplirsen is targeted to DMD patients with a specific genetic mutation, I think the implications for all DMD patients with related genetic mutations are clearly evident."
Sarepta's latest announcement follows 36-week trial results announced on July 24, 2012, which showed that participants treated with a high dose of eteplirsen for 36 weeks were able to walk 69.4 meters (227.7 feet) farther on a six-minute walk test compared to the placebo/delayed treatment group.
MDA has been supporting basic research in exon skipping as a strategy for treating DMD since the 1990s. The strategy coaxes cells to "skip," or ignore, segments (exons) of a gene and piece together the remaining instructions in a way that allows production of a functional protein, such as dystrophin.
The Association gave supplemental support for this eteplirsen trial through a grant to Mendell, a longtime MDA research grantee and co-director of the MDA clinic at Nationwide.
(Note: These results were published online Aug. 1, 2013, in Annals of Neurology. The abstract is available for free, and the entire paper is available for a fee or with a subscription.)