Report from MDA's Scientific Conference 2013

PPMD President Pat Furlong and Vice President of Research Sharon Hesterlee are attending MDA’s Scientific Conference this week in Washington, D.C. Most of what was presented are results that were previously announced. However, there were some interesting presentations, as well as, results worth repeating, that we wanted to share. Sharon and Pat will continue to blog from the conference:


From Pat Furlong

Interview with Thomas Voit

While the content of the MDA meeting was wonderful,  it was equally important to engage in sidebar conversations with leaders from academia and industry.  Thomas Voit, MD is from France.  He has been in the field for many years and is clearly one of the most experienced and influential people in Europe.  We discussed a field that has changed and grown over the last 15 years, with projects seeded long ago with the hope that many would move into clinical trials and hopefully approvals.  Thomas will be speaking later this afternoon about the Prosensa/GSK phase 2 data. Sharon will provide her notes from that presentation.


We agreed competition in the field is good and that both backbone chemistries have established proof of concept in clinical studies.  Having observed Duchenne for many years, we agreed that it would be useful to have two exon-51 skipping drugs approved as we know patients deserve  opportunities/ choices and that some patients might respond better or worse to a particular chemistry. Likewise, competition may lead to discussions around pricing of medicines and improve access for all.


And we agreed, the earlier we treat, the greater likelihood for clinical benefit. We will have to ask what FDA/EMA will require in order to treat neonates and/or very young children, which comes full circle to our efforts around newborn screening.


With a smile, Thomas said that both chemistries work, that side effects can be managed, and that he thought if he was able to treat a baby with one of the existing chemistries, he believes that child might continue to walk into their 20s. We agreed it has been slow in coming, (15 years!) but this progress is a big and welcome step nonetheless.

Read GSK's Press Release Announcing Their Latest Results

Continued Access to Drisapersen for Patients Completing the US Ph I...


Jerry Mendell, MD

  • 74 week data
  • First 12 week dose, 2 placebo and 4 high dose - no dystrophin
  • 24 week time point - dystrophin in 30 mg/kg
  • 48 wk - dystrophin found in all patients' biopsies
  • 8 patients 30-60% dystrophin expressed
  • Patients who rolled over from placebo are also producing dystrophin
  • At 48 wk. 47% increase of dystrophin in all patients on compound for 1 year. Placebo/roll over dystrophin produced.
  • Progressive increase from earliest time point through 48 weeks compared to control.
  • nNos binding site restoration in some patients at 48 week time point (functional marker for dystrophin).
  • 6MWT (six minute walk test) - stability in patients who received eteplirsen for up to 74 weeks. Placebo delayed treatment - rolled over at 24 week, continued to decline until 36 week time point, and after stabilized. He believes this coincides with dystrophin expression.
  • Suggests after 12 weeks of dystrophin production, patients stabilize.
  • Two patients dropped off very early and were too far along to receive benefits of treatment.
  • Commented that 6MWT is reproducible.
  • Safety profile - comprehensive laboratory monitoring showed no evidence of toxicity.
  • No single dose missed in 74 weeks of IV dosing. No adverse events. No discontinuations. One patient has transient proteinuria, but cleared within 24 hr.
  • Patients in high dose remained stable at baseline to 74 weeks.

Read Sarepta's Press Release Announcing Their Latest Results

Vascular delivery gene therapy

  • Found that revertant fibers in early study found that these fibers could result in new epigenetic epitopes. This was totally unexpected.
  • In preparation for future gene therapy trials, will look at immune markers and the impact of steroids.
  • Patients who were steroid naive showed a t-cell response in 50%.
  • In steroid users, only 20% had immune response.
  • There was no difference in immune response related to age.
  • Moving forward on a vascular delivery gene therapy trial/mi ro dystrophin and will soon file an IND.
  • Primate delivery, limb delivery, shows 80% gene expression.


From Sharon Hesterlee


Edward Connor (Children’s National Medical Center) presented:

  • Goal was to identify a drug that works as well or better as standard steroid treatment with improved safety profile.
  • Screened for compounds that act like steroids by tamping down two different inflammatory pathways, while avoiding the gene activation pathways associated with classic prednisone side effects; selected “VPB15.”
  • Tested the lead compound in a couple of different inflammatory disease models where it seemed to be active in each case in reducing inflammation.
  • In the mdx mouse model (mouse lacks dystrophin) the compound was either better or comparable to prednisone treatment in increasing strength; however, VBP15-treated mice did not show the stunted growth or increased signs of muscle degeneration that are seen in steroid-treated mice.
  • Believes that VBP15 is anti-inflammatory without suppressing the immune system.
  • What’s next?  The compound has moved into the preclinical studies required to lay the groundwork for a clinical trial; the National Institutes of Health TRND program and MDA have supplied funding; the company is now planning for a pre-IND application meeting (Investigational New Drug) with the Food and Drug Administration and may be in the clinic by late 2013 or early 2014.
  • Clinical plan:  short phase I study to look at safety and kinetics of drug metabolism; phase 2a study to look at safety and dosing; phase 2b to test selected dose, and then phase 3 definitive trial for drug approval.

Lisinopril vs. Losartan (Cozaar) Study Update

Hugh Allen, Ohio State University

Investigators, led by Dr. Hugh Allen, compared the ability of lisinopril and losartan to improve cardiac function and skeletal muscle strength.  Both lisinopril and losartan are cardiac drugs, but they work in different ways and there is some evidence from earlier mouse studies that losartan may improve muscle strength.  At the end of one year investigators were able to tell that both drugs were equally effective at improving cardiac function with about the same side effect profile; however, no conclusions were able to be drawn about muscle strength function for either drug because not enough data was collected.

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Comment by Sharon Hesterlee on April 25, 2013 at 2:38pm

Ofelia--he didn't go into that much detail (as far as correlating nNOS binding restoration with particular dystrophin outcomes).  It was almost entirely the same information that Sarepta has already presented--I don't think he was allowed to say much extra. 

And Juan, I don't recall any of the speakers mentioning PRO-044.  I did convey the message to Prosensa that people are asking about this study and the results. 

Comment by Ofelia Marin on April 25, 2013 at 1:10pm

 Could you please give me more details about this for Eteplirsen "nNos binding site restoration in some patients at 48 week time point (functional marker for dystrophin)." I know that nNOS binding is somewhere around R16, R17. Have they noticed that the ones preserving R16-17 are the ones with nNOS restoration, as expected?

Comment by JUAN PEDRO ARBULU on April 25, 2013 at 1:06pm

Thank you for the notes.

Was there something about PRO 044 ?

Comment by Sharon Hesterlee on April 25, 2013 at 12:29pm

So, actually your question was about treatment over time and I don't have detailed enough notes to answer that question, but certainly the stunted growth you see in steroid-treated mice (and not in VBP15-treated mice) would suggest that your explanation fits.

Comment by Sharon Hesterlee on April 25, 2013 at 12:27pm

Hi Amit--so basically the drug didn't show some of the specific negative effects you see with prednisone (prednisolone actually) in the mdx mouse.  Steroids don't work as well in the mdx mouse as they do in humans although it's difficult to compare them directly, and that might be because of the negative impact of steroids on muscle growth in the mdx mouse.  VBP15 in the mice did not seem to activate the pathways that cause negative steroid responses in the mdx mice and did activate the more positive ones.  The group also showed x-rays of bones of mice treated with VBP15 and with prednisolone--the prednisolone-treated mice had significantly shorter leg bones than those that received VBP15.


Comment by amit gupta on April 24, 2013 at 2:06pm
Thanks, Sharon.

When you get time, can you please clarify what is meant by "the compound was either better or comparable to prednisone treatment in increasing strength; however, VBP15-treated mice did not show the stunted growth or increased signs of muscle degeneration that are seen in steroid-treated mice"..?

Does this mean that VBP15 not only increased strength initially as does prednisone, but it also preserved the muscles which prednisone does not, and therefore VBP15 maintains the increased strength for much longer period?

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