Join our online Q&A on exon skipping

As for the family relocating to Europe. I believe Sarepta has a planned phase III trial for exon 53 in several EU countries but more information should come from them. Biomarin was also recruiting into their phase I/II studies, so you should check which are the trial sites for Biomarin in Europe

Twinless wrote:

Thanks so much for the doing this Q&A session! I am Leslie Guzmán, the mother of Diego Ramirez with Duchenne, he´s 11 years old and he’s walking. He has deletion 48-52, so he needs Exon 53. My question is – my husband is getting transferred with P&G to Europe. We can pick from Switzerland or UK. Could he join the trial under way that you are running?

Leslie

We currently have plans to initiate the exon 45/53 (ESSENCE) Trial in UK in the near future. Currently no study sites are planned for Switzerland.

Laura Jacobs wrote:

Hi everyone!

A question from Rachel Halpin in Liverpool whose son, Harry, has Duchenne muscular dystrophy:

When will clinical trials take place for exon 44?

Exon 44 is one of our future exons that we are working on; however, we have not yet determined the timeline for exon 44 clinical trials.

williamdmd wrote:

Hello,

My son William was recently diagnosed with Duchenne Muscular Dystrophy. William has exon deletion 45-52. I am looking into all research which could possibly help with his condition. I am aware this is focused on exon 51. Could you inform me whether this treatment is something that could help William’s deletion in future or does he have too many exons deleted?

Many thanks,
Caroline Calvert

Based on the 45-52 deletion, your son would be amenable to exon 53 skipping. We recommend that you discuss this with your physician to discuss potential treatment options for your son. We are planning exon 45 and exon 53 trials in the US and EU later this year.

From the message from Nick who raises a number of important poitns

NickCatlin wrote:

Why are measures against placebo not showing an effect even after 48 weeks?
THIS IS NOT SO SURPRISING AS DYSTROPHIN RESTORATION PER SE DOES NOT MAKE CHILDREN MUCH STRONGER BUT ONLY PROTECTS MUSCLE FROM FURTHER MUSCLE DEGENERATION. AS YOU SAID BEFORE, STEROIDS AND OTHER TREATEMENTS HAVE HELPED TO STABILISE DISEASE PROGRESSION TO SOME EXTENT. SO IN A RELATIVELY SHORT PERIOD OF TIME, 48 WEEKS, IT CAN BE CHALLENGING TO IDENTIFY A CLEAR DRUG EFFECT

What is the agreed ethical time limit for continuing the use of placebos in Duchenne trials?
THIS IS ALSO A VERY GOOD QUESTION. THE LONGEST STUDIES WITH A PLACEBO ARM AND HOWEVER A CROSSOVER, WITH ALL PATIENTS RECEIVING AN EFFECTIVE THERAPY AT SOME POINT, IS A PFIZER STUDY ON A COMPLETELY DIFFERENT MOLECULE. THIS STUDY HAS A 2 YEARS PERIOD OIN WHICH SOME CHILDREN WILL RECEIVE PLACEBO. THIS WOULD NOT BE APPLICABLE
STUDY DESIGN FOR DMD BOYS. SO THE QUESTION IS TO THE ADVOCACY GROUPS AND PARENTS, WOULD THEY ACCEPT A PLACEBO CONTROLLED STUDY OF 2 YEARS? OF 3 YEARS? OR LONGER?
How will trial design recognise that Duchenne patients now take a range of drugs and use physical management interventions that could also influence clinical outcomes?
BY HAVING LONGER STUDIES

Are the 6MWT and NSAA valid and reliable measures of clinical benefit?
THEY HAVE BEEN USED BEFORE. THE PTC STUDY DEOMONSTRATED BENEFIT IN THE SUBSET OF BOYS WITH 300-400 METRES IN BOTH 6MWT AND NORTH STAR. AND SIMILAR DATA WERE PRESENTED BY SRAPTA AT FDA IF MY MEMORY IS CORRECT

Two questions for Sarepta:

1) If the FDA refuse approval of eteplirsen, what impact will this have on follow on exon skipping drugs?

2) If it is approved by the FDA, how likely is it that the closest follow on exon skipping drugs for 45 & 53 will move through the approval pathway at a faster rate than eteplirsen?

Dystrophin as a biomarker in future clinical trials.
We apprectiate that muscle biopsies are invasive and , while we work hard to minimise risks, there is always a small risk associated with the procedures. When developing a new drug however as exon 53 in SKIP NMD, however we felt essential to assess if the drug (after a period of 48 weeks, so when the children in the eteplirsen study all had dystrophin expression) is working in the way we anticipate it to work. It might not be necessary to do muscle biopsies in each and every study, but at this stage of development this is still providing the investigators and the company essential information. We and Sarepta have taken a very great care in esnuring that problems encountered in rpevious trials with loss of samples and so on, do not occurr in current and future studies

Another question from one of our supporters whose son has Duchenne muscular dystrophy:

I’ve read that participation on a trial for SMT C1100 is an exclusionary criterion for exon skipping trials – is this for a specific period of time or is a child to be excluded if they have ever taken part in a SMT C1100 trial and if so, why?