DMD: Eteplirsen Data Still Encouraging After Three Years

Boys with DMD continuously treated with eteplirsen for three years walked farther in six minutes than those receiving a placebo for the first six months

Article Highlights:
  • Boys with DMD who were treated continuously with Sarepta's exon-skipping drug eteplirsen walked farther in six minutes after three years than those who had received a placebo for the first six months of the study; continued stabilization of respiratory muscle function also was reported.
  • MDA is not funding this study, but principal investigator Jerry Mendell is a longtime MDA research grantee and directs the MDA clinic at Nationwide Children's Hospital in Columbus, Ohio.
  • Sarepta plans to submit an application for approval of eteplirsen to the U.S. FDA in mid-2015; in the meantime, it is conducting a phase 3, confirmatory trial of eteplirsen in ambulatory boys with DMD and a safety study in nonambulatory boys and young men with the disorder.


by Margaret Wahl on January 13, 2015 - 3:36pm

Boys with Duchenne muscular dystrophy (DMD) caused by specific genetic mutations who were treated with the experimental drug eteplirsen for 168 weeks (3.2 years) continued to show an advantage in the distance they were able to walk compared to those treated with the drug for only 144 weeks (2.8 years), although all boys had declined in walking distance since the start of this phase 2b trial of eteplirsen. Cambridge, Mass.-based biopharmaceutical company Sarepta Therapeutics, developer of eteplirsen, announced these and other results in a Jan. 12, 2015, press release.

Eight boys with DMD caused mutations in the dystrophin gene potentially treatable by eteplirsen were given weekly intravenous infusions of the drug for all 168 weeks. Two lost walking ability early, allowing only six to be evaluated on the "six-minute walk test" in later assessments.

Four boys with DMD and eteplirsen-treatable mutations received placebo infusions for the first 24 weeks, followed by eteplirsen infusions. These are referred to as the "placebo/delayed treatment" group.

At week 168, the six continuously treated boys showed an average decline in their six-minute walking distance of 76.7 meters (252 feet) compared to their baseline measurement. The boys in the placebo/delayed treatment group experienced an average decline in walking distance of 142.1 meters (466 feet). At week 168, those who were continuously treated could still walk 65.4 meters (215 feet) farther in six minutes than those who were not treated until week 25.

Respiratory function was also measured from baseline through week 168. When scores from all 12 trial participants (in both groups, including those no longer walking) were evaluated, they showed average increases in respiratory measurements known as maximum inspiratory and expiratory pressure (MIP and MEP), as well as an average increase in forced vital capacity (FVC), a measure of lung volume. However, there was a slight decline in the average "percent of predicted" (percent of normal) for scores for all these measurements, indicating that the DMD-affected boys were beginning to fall behind their healthy peers in respiratory function over the course of the study. Sarepta says the assessments indicate "continued stability of respiratory muscle function."

Neurologist Jerry Mendell, co-director of the MDA clinic at Nationwide Children's Hospital in Columbus, Ohio and a longtime recipient of MDA research funding, was the principal investigator on the eteplirsen study (although the study is not funded by MDA).

"With greater than three years of eteplirsen experience, the clinical outcomes that our team has demonstrated in the testing of these boys exhibit greater stability in function than anticipated at a time when we often observe a more significant decline without treatment," Mendell said. "Based on my many years of caring for patients with this devastating disease, I view these more than three years of data as very encouraging."

He added, "The safety profile of eteplirsen continues to impress me. We have not witnessed any clinically meaningful treatment-related adverse events during the 168 weeks of eteplirsen treatment."

Eteplirsen targets exon 51 of the dystrophin gene

Eteplirsen is an "exon-skipping" compound, designed to target and block (skip) a section of the gene for the dystrophin muscle protein known as exon (section) 51. The goal is to make cells splice together the surrounding exons (sections) of genetic instructions and produce a shorter-than-normal, but functional, dystrophin protein. Increases in dystrophin protein levels were seen in this study when muscle biopsies were examined at week 48.

Sarepta says mid-2015 NDA submission is planned for eteplirsen

Sarepta says its plan for a mid-2015 new drug application (NDA) submission to the U.S. Food and Drug Administration (FDA) for market approval of eteplirsen remains unchanged and will continue to be evaluated based on discussions with the FDA and as additional data become available. The drug could receive an accelerated approval from the agency, meaning a temporary approval while awaiting the results of a large-scale, phase 3 trial. Or, the FDA could request the results of a completed phase 3 trial before considering the drug for approval.

The company also says it hopes to initiate trials for exon-skipping compounds targeting exons 45 and 53 later this year.

Phase 3 trial in ambulatory boys remains open

A 160-participant, phase 3 trial of eteplirsen is open at 39 U.S. sites in boys with DMD who are 7-16 years old, able to walk more than 300 meters (984 feet) in six minutes, and meet other study criteria. For details and contact information, see Confirmatory Study of Eteplirsen in DMD Patients; or enter NCT02255552 in the search box at

Safety study of eteplirsen in advanced DMD open

In addition to the phase 3 trial in ambulatory (walking) boys with DMD, Sarepta is conducting a 20-person study to explore the safety of eteplirsen in boys and young men with DMD who are 7-21 years old, are not able to walk at least 300 meters (984 feet) in six minutes and meet other study criteria. For details and contact information, see Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy; or enter NCT02286947 in the search box at

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