FDA Approval of Exon Skipping
I realize that this is a little premature, but since I have a 10 year old who is predicted to benefit from skipping either exon 43 or 45, but not 51, I am more than a little concerned that he'll be on a ventilator and gi tube before completion of clinical trials for a compound that will skip exon 43 or 44. I spent a godawful amount of money on a book on FDA law, and reached the conclusion that the FDA probably has discretion to treat the Prosensa compounds as one drug, even where they are designed to skip different exons, and the would apply to AviBioPharma's compounds. However, there is nothing in the law that would require the FDA to do so. Does anyone know whether these two companies or any of the patient advocacy organizations have begun talking to the FDA about whether they will require separate trials for each compound? I have heard a great deal of rumor and speculation, but I really want to know whether there is any reason to be optimistic, short of going to Congress for a legislative change. If we need a legislative change, then that ball needs to get rolling next year, assuming that the Phase I/II's for ProSensa and AviBioPharma come in as expected in December and are positive.
Replies to This Discussion
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Permalink Reply by MicahsDaddy on
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questions i ponder is what will happen when they test a larger area of the body or systemically? how will the body react for all those patients who currently have 0% dystrophin who suddenly start making it? will it be treated like a virus and the immune system tries to kill it off?
I assume if so, then they will have an immunosuppressant to go with exon skipping.
but, Utrophin is already in their systems, no need to suppress the immune system.
also, exon 1 and exon 79 deletions will not benefit from exon skipping...what about them? we can't leave them behind.
what about people who can't afford to travel? we can't leave us behind....
maybe start a new charity that will save funds for when people need to fly to another country for care?
sorry if i keep repeating myself....i just believe. for those star wars fans, "The force is strong with this one" lol
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Permalink Reply by Ofelia Marin on
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Shouldn't we look at PTC124 or Jerry Mendell's mini-dystrophin for an answer to this question?
Cossu's stem cell treatment definitely needs immunosuppressants...
MicahsDaddy said:questions i ponder is what will happen when they test a larger area of the body or systemically? how will the body react for all those patients who currently have 0% dystrophin who suddenly start making it? will it be treated like a virus and the immune system tries to kill it off?
I assume if so, then they will have an immunosuppressant to go with exon skipping
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Permalink Reply by cheryl cliff on
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Hi Christian-
I do love those cute little characters you are able to put on the screen.
Regarding all of these upcoming treatements...including utrophin upregulation... no one really knows what will happen with any of this new stuff. But we can't be afraid of any one treatment without being afraid of them all. Duchenne isn't a one size fits all disease and there should probably be several options available for treatment, besides prednisone and deflazicort. I don't think exon skipping is being created in order to leave anyone behind, just as PTC124 wasn't created with the intent of leaving us in the dust. But it has left us in the dust Christian, your kid and mine.
Upregulation of utrophin is behind exon skipping in clinical trials. I am all for upregulation of utrophin but I don't think it will get here first. With a child on the line - time is critical. For those who's child is over the line already, god help them - they should have first option.
As far as nobody being able to travel to other countries for care...realistically speaking...any valid treatment within western civilization, for this terrifying disease, won't be hoarded, not for long anyway. Gee, I can see the legal entanglements already...but then thats what I get for hanging around attorneys for 28 years.
Someday, I want you to show me how to install those little characters.
cheryl
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Permalink Reply by Paul Cliff on
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Christian,
Where does the $250k/treatment number come from? I've heard it before, but I've never been able to trace down the source. If that's a real number, then I don't understand why AviBioPharma and ProSensa are even bothering with the clinical trials. Neither an insurance company, MediCaid nor Medicare would cover that. In Calfornia alone, we probably have at least a thousand, probably more like two thousand DMD patients, which would mean a billion dollars a year, indefinitely. Medicaid and all but the very biggest insurance carriers would go broke.
MicahsDaddy said:here's some not so good numbers for calculations...i apologize in advance:
1. Each exon skipping treatment without insurance will cost $250,000
2. They estimate treatments being needed quarterly.
3. Cost of flights to the UK 4 times a year.
ok, better news:
1. When they get to the exon you need, it will most likely be available here in the US as well.
So, what to do? As I said previously, the cocktail is closer than exon skipping and I honestly feel that our focus and stress should be on that.
Reason I say this is because I want someone who has a deletion that includes either the very 1st exon or the very last exon to be saved (exon skipping wont help them) as much as i want my own son to be saved. That said, my son needs exon 46 skipped, which is right there with regards to one of the first few that they will test against. But, if the cocktail was ready before hand, then none of us would need skipping.
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Cheryl,
Utrophin upregulation (assuming that it works in humans) has the potential to get to market soon enough, sooner than exon skipping in my opinion. As you might know, Summit made a deal with BioMarin (pharma company located in CA). BioMarin will start clinical trials in 2009. If you look at their webpage you'll note that they have experience with bringing drugs for orphan diseases to the market. Their latest drug was approved in 3 years.
The question that remains is how much benefit that small molecule will bring to our boys... it worked fine in mice but as we all know their DMD is a lot less severe.
Ofelia
cheryl cliff said:Hi Christian-
I do love those cute little characters you are able to put on the screen.
Regarding all of these upcoming treatements...including utrophin upregulation... no one really knows what will happen with any of this new stuff. But we can't be afraid of any one treatment without being afraid of them all. Duchenne isn't a one size fits all disease and there should probably be several options available for treatment, besides prednisone and deflazicort. I don't think exon skipping is being created in order to leave anyone behind, just as PTC124 wasn't created with the intent of leaving us in the dust. But it has left us in the dust Christian, your kid and mine.
Upregulation of utrophin is behind exon skipping in clinical trials. I am all for upregulation of utrophin but I don't think it will get here first. With a child on the line - time is critical. For those who's child is over the line already, god help them - they should have first option.
As far as nobody being able to travel to other countries for care...realistically speaking...any valid treatment within western civilization, for this terrifying disease, won't be hoarded, not for long anyway. Gee, I can see the legal entanglements already...but then thats what I get for hanging around attorneys for 28 years.
Someday, I want you to show me how to install those little characters.
cheryl
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"Where does the $250k/treatment number come from."
Paul, I read it as a quote from someone significant to this type of research. I can't recall who, but it was last year when I thought I had what it took to become a researcher (LOL) that I came across it.
It was not just someone on a message board that pulled it out of their woo hoo and threw it up.
I will try to find it again and send you the link....
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Hi Ofelia,
Thanks, I knew utrophin wasn't far behind but I forgot (middle age does that) it was that close. I guess, when I said exon skipping is closer to reality for my son it is because I am taking in to count the current trials in the UK. I realize this has nothing to do with our FDA system but if it takes too long to get here I will go there.
Now, on to the Biomarin webpage,
cheryl
Ofelia Marin said:Cheryl,
Utrophin upregulation (assuming that it works in humans) has the potential to get to market soon enough, sooner than exon skipping in my opinion. As you might know, Summit made a deal with BioMarin (pharma company located in CA). BioMarin will start clinical trials in 2009. If you look at their webpage you'll note that they have experience with bringing drugs for orphan diseases to the market. Their latest drug was approved in 3 years.
The question that remains is how much benefit that small molecule will bring to our boys... it worked fine in mice but as we all know their DMD is a lot less severe.
Ofelia
cheryl cliff said:Hi Christian-
I do love those cute little characters you are able to put on the screen.
Regarding all of these upcoming treatements...including utrophin upregulation... no one really knows what will happen with any of this new stuff. But we can't be afraid of any one treatment without being afraid of them all. Duchenne isn't a one size fits all disease and there should probably be several options available for treatment, besides prednisone and deflazicort. I don't think exon skipping is being created in order to leave anyone behind, just as PTC124 wasn't created with the intent of leaving us in the dust. But it has left us in the dust Christian, your kid and mine.
Upregulation of utrophin is behind exon skipping in clinical trials. I am all for upregulation of utrophin but I don't think it will get here first. With a child on the line - time is critical. For those who's child is over the line already, god help them - they should have first option.
As far as nobody being able to travel to other countries for care...realistically speaking...any valid treatment within western civilization, for this terrifying disease, won't be hoarded, not for long anyway. Gee, I can see the legal entanglements already...but then thats what I get for hanging around attorneys for 28 years.
Someday, I want you to show me how to install those little characters.
cheryl
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"Shouldn't we look at PTC124 or Jerry Mendell's mini-dystrophin for an answer to this question? Cossu's stem cell treatment definitely needs immunosuppressants..."
Yes, definitly look at Cossu and the MiniDys for ways to get around it....if necessary.
As for PTC-124, I am not exactly sure how to word this correctly. It has something to do with about how the dystrophiin gene is with a nonsense mutation. I believe it is reading the gene properly until it hits that stop, then after that stop, everything is reading normally again. PTC-124 forces it's way through that stop and the exon is complete. I am guessing, please don't quote me on this, that there is already slight dystrophin "somehow" being produced and is in the body at very, very minimal amounts...maybe 1% to 5%. If so, then the immune sysstem won't reject dystrophin from the body.
As you know, with deletions and duplications, you have to remove exons, not push through a road block, to restore the gene partially.
I really wish there was a professional on here that could clear that up for me...us.
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It's from Eric Hoffman. He was talking about the trials they performed in dogs. I don't think this will be even close to the cost of an exon skipping treatment (IF it works). It should be a lot lower. These pharmaceutical companies are in the game for profit... how many patients can afford this price, 1,2? :-)
MicahsDaddy said:"Where does the $250k/treatment number come from."
Paul, I read it as a quote from someone significant to this type of research. I can't recall who, but it was last year when I thought I had what it took to become a researcher (LOL) that I came across it.
It was not just someone on a message board that pulled it out of their woo hoo and threw it up.
I will try to find it again and send you the link....
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some important quotes from this thread:
"Utrophin upregulation (assuming that it works in humans).......it worked fine in mice but as we all know their DMD is a lot less severe."
"...exon skipping treatment (IF it works)."
IF and ASSUMING are huge words here....This is why we can't have all our eggs in one basket....yet.
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Ofelia and Christian-
You guys are extremely smart but do you really believe that a treatment, regardless of who own's it, that will snatch a child from certain death would be denied because of inability to pay? Yea, drug companies are in this for profit, but they can't make much if their customers die. I think they know the moral issues at hand. Besides, if they did behave badly I'd like to see them handle a mob of angry parents in a court room...
We've already seen what a judge will do with this issue and PTC124.
cheryl
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Ofelia, thank you, that helped me find the article:
Click HERE for NY Times article.
"But Eric P. Hoffman, the author of the editorial and director of the research center for genetic medicine at Children’s National Medical Center in Washington, said antisense therapy was expensive. He said he and his colleagues were studying it in dogs with muscular dystrophy and finding it effective. However, the cost for each round of treatment is $250,000, with treatments needed every few months."
Ofelia Marin said:It's from Eric Hoffman. He was talking about the trials they performed in dogs. I don't think this will be even close to the cost of an exon skipping treatment (IF it works). It should be a lot lower. These pharmaceutical companies are in the game for profit... how many patients can afford this price, 1,2? :-)
MicahsDaddy said:"Where does the $250k/treatment number come from."
Paul, I read it as a quote from someone significant to this type of research. I can't recall who, but it was last year when I thought I had what it took to become a researcher (LOL) that I came across it.
It was not just someone on a message board that pulled it out of their woo hoo and threw it up.
I will try to find it again and send you the link....
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