Walking ability and respiratory function in boys with Duchenne muscular dystrophy (DMD) show continued benefit from eteplirsen at 144 weeks (almost three years), the drug's developer announced today. In addition, the intravenously infused drug was well tolerated, with no serious treatment-related adverse events seen.
Eteplirsen is an experimental compound in development by Cambridge, Mass.-based Sarepta Therapeutics to treat about 13 percent of DMD patients — those who have specific mutations (flaws) in the gene for the muscle protein dystrophin.
The goal of treatment with eteplirsen — known as an exon-skipping drug — is to coax muscle cells to reinterpret genetic information for the dystrophin protein so that functional dystrophin protein can be made even though the dystrophin gene is flawed.
MDA has funded the development of exon skipping as a treatment for DMD since the 1990s and continues to fund studies to refine this strategy. MDA contributed $110,000 to the phase 2b trial to help defray travel costs for families, support the processing of muscle biopsy samples, and fund the services of a clinical evaluator.
Sarepta reported the 144-week results from its phase 2b extension trial of eteplirsen in a July 10, 2014, press release. Previously, results on walking ability — measured by the distance walked in six minutes — and respiratory function were reported at 120 weeks in January 2014.
About the 144-week extension study results
Of the 12 participants in the original phase 2b trial of eteplirsen, 10 were still able to perform the six-minute walk test at 144 weeks. (Two lost walking ability early in the study.) Of these 10, there were six who received weekly intravenous infusions of eteplirsen throughout the 144 weeks, and four who received a placebo for the first 24 weeks, followed by eteplirsen treatment (the “placebo-delayed treatment” group).
The continuously treated trial participants experienced a decline in six-minute walking distance of 33.2 meters at 144 weeks compared to their baseline (initial) walking distance. (A meter is about 3 feet.)
Those in the placebo-delayed treatment group lost 68.4 meters in walking distance from baseline to week 36 and then 39 meters from week 36 through week 144, for a total decrease in walking distance of 107.4 meters from baseline to week 144.
The 144-week difference in six-minute walking distance between the continuously treated group and the placebo-delayed treatment group was 74.2 meters, which was statistically significant and suggests a benefit for continuous treatment with eteplirsen.
The average six-minute walk distance in both groups was greater than what would be expected from the natural history of untreated DMD.
Average respiratory function test results also showed stabilization. Natural history studies in DMD have shown that at least one respiratory function measure generally declines by about 8 percent per year after 10 to 12 years of age. The boys in the extension study are now an average of 12 years old.
New drug application to be submitted soon
Sarepta plans to submit an application for approval of eteplirsen to the U.S. Food and Drug Administration (FDA) under the agency’s accelerated approval program, which can allow a drug to be distributed to patients prior to its full approval if certain conditions are met and further studies are agreed to.
“We now have nearly three years of treatment experience with eteplirsen from our phase 2b clinical study program and, based on guidance from the U.S. Food and Drug Administration earlier this year, we plan to submit these results along with additional data and analysis as part of a New Drug Application for eteplirsen by year-end,” said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics.
Neurologist Jerry Mendell, principal investigator on the eteplirsen trial and a longtime MDA research and clinical grantee at Nationwide Children’s Hospital in Columbus, Ohio, also was encouraged by the 144-week results. “The long-term clinical data for eteplirsen showing a slowing in the decline of walking ability in a population now on average 12 years old are very encouraging, particularly when compared with the growing body of DMD natural history data which clearly show that similarly aged patients typically experience an increasingly rapid decline in walking ability and lose ambulation in their early teen years,” Mendell said.