DMD: Phase 2 Exon-Skipping Trial Launched

AVI BioPharma has begun phase 2 testing of its experimental exon-skipping drug eteplirsen (AVI-4658) in boys with Duchenne MD

Article Highlights:
  • AVI BioPharma opened a phase 2 trial of its exon-skipping drug eteplirsen (previously called AVI-4658) on Aug. 15, 2011, at Nationwide Children's Hospital in Columbus, Ohio. Three boys with Duchenne muscular dystrophy received infusions; the trial will involve a total of 12 boys with DMD ages 7-13 who are still ambulatory.
  • Study investigators will assess efficacy, safety, tolerability and the way the body metabolizes eteplirsen, which will be administered intravenously at two different doses over a period of 24 weeks.
  • The experimental drug is designed to cause cellular protein-building machinery to "skip over" flawed instructions in a section of the dystrophin gene, prompting the production of partially functional dystrophin protein.
by Amy Madsen on August 15, 2011 - 11:37am

Updated: View MDA's video about the launch of the eteplirsen trial on YouTube.

Biotechnology company AVI BioPharma announced Monday, Aug. 15, 2011, that its phase 2 exon-skipping trial of eteplirsen (AVI-4658) is officially under way at Nationwide Children's Hospital in Columbus, Ohio. Study investigators have administered the experimental drug to the first three trial participants with Duchenne muscular dystrophy (DMD).

Neurologist Jerry R. Mendell of Nationwide Children's Hospital and principal investigator of the study said in AVI BioPharma's press release, "We have seen tremendous promise for eteplirsen to potentially modify the progression of DMD in patients and we look forward to further understanding its potential through this longer study."

Investigators are testing eteplirsen in 12 boys with DMD, ages 7 to 13 years old, who still are able to walk.   

"MDA has been supporting the development of exon skipping since the strategy's earliest days in the 1990s," said neurologist Valerie Cwik, MDA medical director and executive vice president for research. "We're thrilled to see the launch of this trial in the United States."

About the new trial

The phase 2 trial is designed to evaluate eteplirsen doses of 30 and 50 milligrams per kilogram of body weight, administered intravenously, and is double-blinded and placebo-controlled.

This means one group of boys will receive the 30-milligram dose; a second will receive the 50-milligram dose; and a third group will receive a placebo. Neither investigators nor participants will know each person's group assignment until after the study has been completed.

Investigators will assess the drug's effects, safety, tolerability and pharmacokinetics (how the body metabolizes the drug) at both doses. Four boys will be in the 30-milligram treatment group; four will be in the 50-milligram group; and four will make up the placebo cohort.

The trial is being overseen by Mendell, who co-directs the Muscular Dystrophy Association clinic at Nationwide Children's, with AVI BioPharma funding most of the costs of the study. MDA has committed $110,000 in supplemental funding to help defray travel costs for families participating in the study, to support the processing and analysis of biopsy samples, and to fund the services of a clinical evaluator.

Chris Garabedian, AVI's CEO and president, said data from this study is expected around the end of the second quarter of 2012.

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur. MDA has no ability to influence who is chosen to participate in a clinical trial. To learn more, see Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to

For more details, see Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients, or search for NCT01396239 at  

About eteplirsen

DMD involves a complete or nearly complete lack of functional dystrophin protein in the skeletal and cardiac muscles, as a result of any of a large number of mutations in the dystrophin gene.

Eteplirsen is an antisense oligonucleotide that works by encouraging cells to "ignore" ("skip") a section of genetic instructions that contain erroneous information. The cell's protein-building machinery should then splice together the remaining pieces of information, and from these shortened but error-free instructions, synthesize a partially functional protein.

Eteplirsen targets a stretch of genetic instructions in the dystrophin gene called exon 51, and is designed to prompt dystrophin protein production in the muscle fibers of individuals with genetic mutations in or around this exon.

Promoting the synthesis of a truncated dystrophin protein is intended to improve, stabilize or significantly slow the disease process and prolong and improve the quality of life for patients with DMD, the company said in its press release.

The drug apparently is safe and in earlier trials has resulted in skipping of exon 51 and dystrophin production in several trial participants. (See Eteplirsen (AVI-4658) Boosts Dystrophin Production in DMD.)

That eteplirsen resulted in dystrophin production when given intravenously is significant, as delivery directly to muscles via injections would be cumbersome and uncomfortable for recipients.

Meaning for people with DMD

Exon skipping is a promising therapeutic strategy for people with certain types of mutations that cause DMD.

If eteplirsen is proven to safely and effectively skip exon 51, exon-skipping drugs can be developed for other DMD-causing mutations and possibly for other neuromuscular diseases as well.

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