Boys with Duchenne MD due to specific mutations showed continued stabilization of walking; those treated throughout the study walked farther than a delayed-treatment group
|Update (Sept. 26, 2013): Results through 96 weeks showed a continued stabilization of walking distance in boys treated with eteplirsen. Earlier results showed that infusions of eteplirsen for 48 weeks resulted in a statistically significant increase in the production of dystrophin protein.
Sarepta Therapuetics reported the 96-week results in a Sept. 26, 2013 press release. Sarepta President and Chief Executive Officer Chris Garabedian said, “We look forward to sharing these updated data with the FDA as part of our New Drug Application for eteplirsen, which we plan to submit in the first half of 2014.”
Eteplirsen, an experimental exon-skipping drug designed to treat Duchenne muscular dystrophy (DMD) caused by specific mutations in the dystrophin gene, continues to show sustained benefit on walking distance through week 84 of a phase 2b, 12-person study.
Eteplirsen is designed to skip exon 51 of the dystrophin gene.
A webcast of the conference presentation, with supporting materials, is available on the Sarepta website.
"We now have demonstrated stability of walking for over a year and a half in the original eteplirsen treatment cohort in boys who are now 11 years old on average, an age when many DMD boys have lost the ability to walk," said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics.
Walking distance, dystrophin production evaluated
After 84 weeks (1.6 years), walking ability stabilized in all trial participants, although those treated with eteplirsen for all 84 weeks stabilized at a higher level (longer walking distance) than those who were on a placebo for the first 24 weeks and then treated with eteplirsen.
Walking distance was measured by the six-minute walk test — how far a trial participant can walk in six minutes.
Participants treated with weekly intravenous infusions of eteplirsen for the entire study period at either of two dosage levels are designated the continuous treatment group. Participants treated with placebo infusions for the first 24 weeks, followed by eteplirsen infusions, are designated the placebo/delayed treatment group.
Muscle biopsies to assess production of dystrophin — the muscle protein that's needed but missing in DMD — were performed at week 48 in all participants. Results reported earlier showed all participants were producing dystrophin at the 48-week time point.
Two participants from the continuous treatment group lost walking ability by week 24 and therefore could not be evaluated on the six-minute walk test after that point.
One participant from the placebo/delayed-treatment group temporarily lost walking ability due to an ankle fracture and could not perform the six-minute walk test at week 84. He has since regained the ability to walk.
Walking stabilized despite advancing age
The investigators found the following, using data based on the maximum six-minute walking distance that each boy achieved when the test was performed on two consecutive days.
In the continuous treatment group, the decline in the distance walked in six minutes over the course of the study was 21 meters (69 feet). For the placebo/delayed-treatment group, the decline was 67 meters (221 feet). Both groups showed general stabilization (holding steady) of walking ability after week 36, although the continuous group stabilized at a higher level than the placebo/delayed-treatment group. Image courtesy of Sarepta Therapeutics
All trial participants declined in the distance walked in six minutes from the start of the study through week 84 (column 5). However, between weeks 36 and 84, declines in walking distance were less than 10 percent for all participants (column 6). Image courtesy of Sarepta Therapeutics
Sarepta's regulatory path forward
In his presentation at the Wells Fargo conference, CEO Chris Garabedian said the following:
For more information
To learn more about exon skipping and eteplirsen, also read: