Eteplirsen, an experimental exon-skipping therapy 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 74 of a phase 2b, 12-person study.
Eteplirsen is designed to cause skipping of exon 51 of the dystrophin gene.
Sarepta Therapeutics, a Cambridge, Mass.-based biotechnology company, announced the results in an April 5, 2013, press release. Further details will be presented at the MDA Scientific Conference to be held April 21-24 in Washington, D.C.
"We are encouraged to see a continued stabilization of walking ability in patients treated with eteplirsen for nearly one-and-a-half years," said Chris Garabedian, president and chief executive officer of Sarepta.
"These data are particularly compelling when viewed in the context of published natural history studies, which showed substantial declines on the six-minute walk test [the distance walked in six minutes] over this time frame in a similar ambulatory DMD population. These results continue to support the potential of eteplirsen to be a major advance in the treatment of DMD in altering the course of this progressive and irreversible muscle disease."
MDA has been supporting development of exon skipping as a strategy for DMD since the 1990s and provided supplemental funding for the clinical trial of eteplirsen to neurologist Jerry Mendell at Nationwide Children's Hospital in Columbus, Ohio.
At 74 weeks — about a year-and-a-half — weekly intravenous infusions of eteplirsen continued to be well-tolerated, with no clinically significant treatment-related adverse events, serious adverse events, hospitalizations or discontinuations.
One participant experienced a temporary elevation of urinary protein, which resolved and resulted in no clinical symptoms. The participant continued treatment without interruption and remained free of urinary protein through week 74.
Six trial participants who received either 30 milligrams per kilogram per week or 50 milligrams per kilogram per week throughout the study period walked, on average, further in six minutes than the “placebo/delayed treatment group” — four participants who received a placebo for the first 24 weeks, followed by eteplirsen at either 30 or 50 milligrams per kilogram per week for the remainder of the study.
At the 74-week time point, the average decline in the six-minute walking distance in the eteplirsen-treated group (six boys) was 2.2 meters (7.2 feet), while in the placebo/delayed treatment group (four boys), average walking distance in six minutes declined by 64.6 meters (211.9 feet).
The 62.4-meter (204.7-foot) difference in average decline in distance walked was statistically significant.
Two trial participants in the 30 milligram-per-kilogram dose group showed rapid disease progression and lost walking ability by week 24. They therefore could not be included in six-minute walk test results after that point — leaving a total of 10 trial participants whose walking ability could be measured.
In January, Sarepta announced its intention to meet with the U.S. Food and Drug Administration (FDA) during the first quarter of 2013 to discuss next steps for eteplirsen development.
MDA will report results of that meeting when they become available.
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