This morning, AVI BioPharma released information discussing their findings thus far in their Phase IIb study of Eteplirsen.

About Eteplirsen

Eteplirsen uses AVI’s phosphorodiamidate morpholino oligomer (PMO)-based chemistry to skip exon 51 of the dystrophin gene. By skipping exon 51, eteplirsen may restore the gene’s ability to make a shorter, functional form of dystrophin.

The Study

The Eteplirsen Phase IIb Study is being conducted at Nationwide Children's Hospital in Columbus, Ohio. Twelve boys between 7 and 13 years of age eligible for treatment with an exon-51 skipping drug received either IV infusions of placebo (n=4), 30 mg/kg of eteplirsen (n=4), or 50 mg/kg ofeteplirsen once weekly for 24 weeks (n=4). Muscle biopsies for evaluation of dystrophin were obtained at baseline for all subjects, after 12 weeks for patients in the 50 mg/kg cohort and after 24 weeks for patients in the 30 mg/kg cohort. Following the placebo trial, all patients were placed into the open label study.

In the open label study, two placebo patients were randomized to the 30 mg/kg cohort (now n=6) and two placebo patients were randomized to the 50 mg/kg cohort. The open label trial extension trial is ongoing. An extension has just been added to the study, which includes muscle biopsies at 24 weeks and 40 weeks in both the 30 mg and 50 mg cohorts.


Results have demonstrated the following:

  • The group receiving Eteplirsen 30 mg/kg/week over 24 weeks resulted in a 22.5% increase in dystrophin on muscle biopsy, exceeding the company’s expectations. There was no increase in dystrophin in the placebo group.
  • The group receiving Eteplirsen 50mg/kg/week did not show an increase in dystrophin at 12 weeks, despite the higher dose.
  • The dystrophin produced appears to be new, novel dystrophin producing muscle fibers of normal length and consistency. The dystrophin appears to be diffusely distributed throughout the muscle biopsy.
  • There was no change in the clinical outcomes (6 minute walk test, Gower’s maneuver, 10 meter run) in the treatment group at 12 or 24 weeks.
  • Doses were well tolerated and there were no serious side effects to the drug at either doses.


These findings show that:

  • Shorter duration of treatment with eteplirsen (12 week) did not increase novel dystrophin production
  • Longer duration of dosing (at least longer than 12 weeks) is required before meaningful levels of dystrophin are produced
  • Although the amount of dystrophin was increased, the extension study will demonstrate whether or not longer treatment improves clinical outcomes (6 minute walk test, Gower’s maneuver, 10 meter run)
  • The extension study and additional biopsies will also demonstrate whether the amount of dystrophin in the muscle reaches a steady state (for example, does not go beyond 22.5% increase) or if it continues to accumulate and increase


AVI is to be commended for their dedication to Duchenne research and to be congratulated on their current findings.  We are pleased to be partners in their continued research. Eteplirsen is the first DMD specific drug to demonstrate production of new, novel dystrophin consistently throughout the muscle. This extremely important finding supports the need for a pivotal trial. AVI is in the process of producing a brief for the FDA, collating the remainder of their data and presenting the need for next steps. A comprehensive summary of their findings will also be presented at the annual American Association of Neurology meeting in New Orleans, April 25, 2012, during the Emerging Science session.


Kathi Kinnett, Director of Clinical Care
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Comment by Mindy Cameron on April 11, 2012 at 7:03pm
As for skipping duplications, is it possible that, if and when, multi-exon skipping strategies are developed, duplication mutations MIGHT be amenable to skipping in order to get the mutation in-frame? What's the status of research into skipping multiple exons?
Comment by MarcosDad on April 7, 2012 at 10:38am

They don't know exactly how many weeks before the 22.5% dystrophin levels was reached since they found that levels at 24 weeks.  They know it wasn't at 12 weeks because there wasn't any new dystrophin produced, so all we know it could have taken 22 weeks to get to that level and of course you don't expect a clinical result of having dystrophin in your body for 2 weeks.  Bottom line, they need to keep it up for a year or two to see the outcome in my opinion.  These studies are too short to see how anything effects the body since this is a progressive disorder.  When people get atrophy from being in a cast for a long time it takes a long time of PT to recover, I don't see why they think it would be different for DMD.  Also these tests are macro level tests.  10 Meter run - really for a DMD child?  My son had different times on that run during the same checkup.  So was he improving then getting worse then improving all within minutes?  It took 3 years of averaging and plotting these macro level tests for the doctors to say it can't be DMD that my son has because he is not deteriorating.  So as you can see when I read 24 weeks I get frustrated because I've been thru these clinical tests to say one way or another there is an outcome and it was much much longer than 24 weeks.

Comment by Moein on April 7, 2012 at 8:56am

The produced Dystrophin didn,t improve  clinical outcomes!!!!What does this mean?

Back to the article published says:DMD is a stem cell disease!!!!!!!!!!!!

I am afraid that the problem is not only the Dystrophin.


Comment by Ofelia Marin on April 4, 2012 at 1:08pm

Actually, I was not correct when stating "16-29% dystrophin", it is the % of dystrophin positive one would compare that with the 60-100% fibers obtained by Prosensa if those numbers are actually correct. Keep in mind Prosensa did not do a before and after so hard to say if those 60-100% numbers are new fibers. All I can say at this point is to wait and see what happens by week 48...Jury is still out on this one.

Comment by Liisa Underwood on April 4, 2012 at 8:28am
Ofelia, I really appreciate your explanation. I knew I somehow missed something.
Comment by Ofelia Marin on April 3, 2012 at 3:07pm

Never mind, Mindy actually answered my question. Thanks Mindy!

"Prosensa's biopsy data wasn't after 12 weeks of treatment. It was from biopsies that were 2 and 7 weeks post 5 week treatment phase, so the 15% that they got as a high in dystrophin expression after only five weeks of data. That's why Prosensa got clinical improvement earlier than AVI - they produce dystrophin much earlier."

Comment by Ofelia Marin on April 3, 2012 at 2:54pm

This is what I mean. How is this possible: more dystrophin in all 4 boys compared to the boys in the Prosensa/GSK extension but no improvement while the boys in Prosensa/GSK improve? Are these % dystrophin comparable, is 22.5% dystrophin-positive fibers as a percentage of normal comparable with the max 15.6% below? Are the "no improvement" results as a group meaning no statistically significant improvement compared to placebo? Can anyone clarify this?



24 weeks produces 16%-29% dystrophin-positive fibers as a percentage of normal (compared to no increase in the placebo group) in the 4 boys at 30 mg and apparently no improvement.



New dystrophin expression was observed between approximately 60% and 100% of muscle fibers in 10 of the 12 patients, as measured on post-treatment biopsy, which increased in a dose-dependent manner to up to 15.6% of the expression in healthy muscle. After the 12-week extension phase, there was a mean (±SD) improvement of 35.2±28.7 m (from the baseline of 384±121 m) on the 6-minute walk test.


Comment by Ofelia Marin on April 3, 2012 at 1:52pm

Lisa, we need to see some improvement/gain in strength tests, even if not significant as a group and not in all boys, when dystrophin is present. GSK did see increase in 6MWD with variation from boy to boy and some boys still declining. I do not see why results will be different here. It takes longer time for AVI dystrophin to accumulate it seems, but at 24 weeks 30 mg group had 16%-29% dystrophin. Hence i would expect to see some of these boys improving as they did in the Prosensa/GSK trial. AVI's results also mention that the placebo group did not decline so one cannot say that the drug kept the treated group stable since the placebo group did not decline either. It takes longer time, I get it. What I do not get is how they have more dystrophin at 24 weeks than the Prosensa open label extension group at 12 weeks and Prosensa reported increase in 6MWD (at 12 weeks) while AVI did not (at 24 weeks).

Comment by Donna Cicardo on April 3, 2012 at 11:28am

Pat, Thanks for your response.  This is what my worst thought was.  Since it sounds like exon skipping will probably  not work for my son, which drug study should I be watching.  We were hoping to be in the cialis/viagra study that is coming up, but waiting to hear, hoping that more oxygen blood flow would improve his symptoms.  What about the other studies, what are your thoughts.  I know we need to follow the studies on the heart function.  Thanks again for answering my question.  it is really confusing at times, trying to understand all these terms and such.  also, from what I understand, dupliation of exon 2 means that we have a "severe beckers" as we are diagnosed with BMD. 

Comment by Karen O. Burch on April 3, 2012 at 10:42am

Was there a change in the caregiver perception of how their son was doing.  Is this being measured?

Results are so promising.  My prayers continue.

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