FDA states Exon cocktail must go through clinical trials for each exon!

I read that FDA is putting a hold on exon skipping. FDA is now requiring that each exon goes through clinical trial. We were hoping beyond hope that all exons would be approved without each exon formulation having to go through the clinical trial. If you are unfamiliar with the clinical trial process, then google it and you will see it takes years and tons of money - money that the drug company itself has to pay for. It's not even about the money right now - it is about the time factor....

Our son has a duplication of 54-57. If DMD is rare and duplications are only 20% of that - then exon trails for duplication of our son's = being so far out in time, if ever at all. How does a parent retain hope? We raise awareness, donate money, research and our life becomes finding a cure....And, now when one is so close, the government steps in and puts on hold on it??? Life is not fair.....And for those boys that do have exon 50 or 51 - they get "the cure" down the line? Tell me - where is faith and hope???

Even a parent who emails and calls the FDA's chief person and can't get compassionate use approved....
Sorry to be negative - but this is one of the few places that parents understand my writings.....
Char Burke
son of Will - age 6 - duplications 54-57

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Where did you get the info that they require each exon to go through clinical trails?

There is a clinical hold on AVI-4658 until the mouse toxicology studies are completed but other than that I did not hear about any decision for other exons.

Take a look at this discussion on Trial Serve - here is the site address. http://forum.trialserve.com/forum/viewthread?thread=1362
Did I miss something? I don't remember reading or hearing that skipping of exon 50 was a success in boys with dmd.
Remember too that exon skipping IS NOT A CURE....it is a stop gap, taking DMD to BMD and it is not for ALL boys. I am more interested in Utrophin and Byglican than Exon skipping...

I think the answer for Exon Skipping is that they will 'skip' big chunks that will affect the most boys. Meaning that no boy gets an optimal, customized skip...Not optimal, but still doable.....

I think it is too early to discuss skipping other exons until we see if skipping 51 works systemically. I mean if it works well enough to provide clinical benefit for most boys "qualified". If the first results of the UK's systemic trial are good, I hope that FDA will lift the hold. We need to keep in mind that AVI-4658 is a PMO and those do not have a good record of working on the heart or diaphragm in mice. As I posted on the Trial Serve, in my oppinion, the fact that in the IM trial the results were only "highly competitive with Prosensa" is not a great success, the dystrophin expression was only 3-15% in Prosensa's IM trial and they used only non-ambulatory patients. So I expected that the PMO would produce a lot more dystrophin taking into account that they had 2 ambulatory patients in the UK trial. I really hope that when they publish the results we will see higher dystrophin expression.

So I think that it is way too early to consider exon skipping successful at this point.

The PPMOs used for skipping exon 50 do work a lot better than the PMOs in mice; they did show higher dystrophin in the heart and diaphragm as well as skeletal muscles and for longer time, could be administered sub cut etc. So I cannot wait to see some PPMO resuts in boys, but unfortunately that trial (skipping 50) starts next year (earliest).


Char Burke said:
Take a look at this discussion on Trial Serve - here is the site address. http://forum.trialserve.com/forum/viewthread?thread=1362
Skipping exon 50 would benefit my son. Do you know where that trial is supposed to start? Is it going to be a U.S. trial?

AVI will conduct the trial. It's based on the work funded by Charley's Fund (http://www.avibio.com/pr/pr354.php). They are working on toxicology now and plan to fill IND before the end of the year - this is my understanding from AVI's recent conference call. It will be using the new PPMOs which gave good results in mice so far. AVI did not give other details except that they hope to start it in 2010.


Karen Barnett said:
Skipping exon 50 would benefit my son. Do you know where that trial is supposed to start? Is it going to be a U.S. trial?
I HOPE this is not the case. My son needs exon 11 skipping and god knows when will they be able to do that.
Didn't the FDA guy that spoke at the advocacy conference last year talk about this? Anybody remember the details? I think he was the head of the orphan drug program.

There's a lot of reasons to remain hopeful on the research front. Take a look at the latest Quest magazine, they have a nice summary chart of the ongoing research aproaches. Exon skipping is only one approach, is not a cure, and won't work for everyone. It's fantastic news that we're starting to see progress at all.

I'm also expecting we'll see more dollars available to fund research. It looks like there will be some significant dollars coming from Congress.

"Learn from yesterday, live for today, hope for tomorrow" - Albert Einstein

I wouldn't have my hopes on exon skipping anyway. There are other drugs they are working on that will hopefully help more so than skipping exons. Maybe those drugs mixed with exon skipping may make a better treatment, but exon skipping alone is not a guarantee for a good treatment.

Like Lori mentioned, my intersts are in Utrophin or Byglican, as well as BBIC....and maybe even Losartan.

I have read where BMD can be as progressive as DMD, so with exon skipping, who's to say that for each patient that receives it that they will benefit from it. It may help for some, but possibly not for others.

Anyway, my understanding is yes, all exons that can be skipped need to be tested before the FDA can approve them. I believe that once 51 is proven to be effective, then that one can be approved by the FDA for individuals who need it, then again with 50. I also believe that as the first 6 exons that they test against (51, 50, 44, 46, etc (i don't remember the other 2)) are proven to show success, then the process for the rest of the exons will speed up. For e.g., (and these are just exons i am pulling out my woo hoo) trials will take place simultaneously for exons, 4, 11, 17, 20, 61, etc...

My understanding of things are not 100% accurate, so take them for what they're worth. But I am pretty sure that's how it was explained at conference.
I just re-read the interview with Tim Cote that PPMD posted. http://www.parentprojectmd.org/site/DocServer/Interview_with_Cote.p...

I would love to hear from Pat on this one and for her to give us more understanding on what she thinks is going to take place and what we can do, if anything, and when, to promote the urgency of these trials as well as others.

I personally am tired of the roller coaster ride that all of this information can put us all on. One day there's good news, then no news, then horrible news, then great news and it just gets to be too much with just everyday life of DMD families.
reading back:

"I wouldn't have my hopes on exon skipping anyway."

is a pretty wrong/false statement. my apologies for that. What i was trying to say is not to have all your hopes in exon skipping. Kinda like not having all your eggs in one basket.

Hope for any kind of treatment is needed, even if it may not work for every child. Got to remember that there are some exons that exon skipping will not help, like exon 1 and 79. I don't want to see them left behind. I want my son to have a treatment as well as all other mutations...no one left behind.

That's why my hopes are placed more towards the other potential drugs that are being tested. None are a cure, but all could be a treatment for every DMD patient.

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