Hi--Just wanted to introduce myself.  I joined PPMD in January as the Research and Advocacy Director after 11 years at MDA running their translational research and drug development programs.  At PPMD I'll be further developing work with drug companies, reviewing and growing the main research program and participating in advocacy intiatives.  I will also try to jump in as much as possible to answer questions about research and track down information about new treatments/therapies that anyone hears about.  One of my first projects along this line is to get to the bottom of this stem cell report from Costa Rica.  If anyone posts something that needs a response from me and you don't hear from me, you can always send me a nudge at sharon@parentprojectmd.org.  I'm really excited about the chance to focus exclusively on Duchenne and am looking forward to hearing from all of you.

 

Best Wishes,

Sharon Hesterlee

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Hi Char: I guess it depends on what you want to know about duplications...typically they either throw the gene out of frame or interfere with secondary structure of the gene or protein in some way that is damaging. But I'll check to see what specific information I can find on duplications...there's so much interest in this group in the exact types and consequences of different mutations that it would probably be worthwhile to try to put together some materials on this topic for the Web site.

Char Burke said:
Hi Sharon - It's great to have your intelligence and know how here at PPMD! I am a mom of a 7 year old with a duplication of 54-57. I often am frustrated at the lack of information about duplications. If DMD is a rare disease and only 10-20% of boys have duplications, that makes it super rare. Any white papers, researchers, web sites you could recommend? I actually sent you a request on Facebook and you recommended reading the Quest issues which I have been doing. You are correct - those are written with the non doctor, researcher in mind and yet get the concept across. I am focusing on care and uptrophin and drugs that would slow down the cardiomyopathy. Again - welcome and we are so thankful to have someone like yourself. Sincerely, Char Burke
Honestly since AVI changed management (which I still think is a good thing) the flow of information has been cut off a bit from that company so I don't know exactly what the current hold-up is for launching the trial in the US or even if the cause of any delays is regulatory. It was originally, which is why they started in Europe. Let me try to get ahold of someone there to see what the current time line is...I'll circle back with Pat to see if she's had any conversations with them that I don't know about yet. I'll also check with my contact at the Office of Orphan Products. I agree that a meeting in the Fall seems a bit too long to wait, but the topic of that meeting will likely revolve around whether each set of oligos will be treated as a separate drug, not whether or not the AVI trial should move forward now.
Sharon

cheryl cliff said:
Hi Mindym

I completely agree with your position and feel the same as you. Alexander is going off his feet soon and we know what comes after that. We too are in a hurry to get something to save our son. My question is for Sharon, with death staring us in the face WHY in the world is it impossible to sked a meeting sooner than next fall? Obviously the FDA isn't getting the urgent message that meetings need to be held NOW in order to save lives this year!!

Mindy said:
Cheryl - I totally get that. I really do. But I feel like I'm looking at a 1 1/2 year window here to get something in his body before he possibly won't get the kind of results that I hope for from exon skipping. We all know that it will work better the earlier the boys can get access.

And I'm tired of being patient. I will not be that parent who watches my dying son saying, "Gee - I wish they had just pushed that drug through the approval process one year faster." I swore when he was diagnosed that I would have no regrets, and that doesn't include waiting passively if it seems there is work to be done. But maybe I just need a sedative.

Sharon - thank you very much for the information. I thought that exact meeting you're describing took place already in London last fall. Why on earth is the FDA planning another one that sounds exactly the same one year later? Was nothing accomplished last fall?
The Office of Orphan Products acts as a sort of ombudsman to represent rare disease therapeutics--they don't have decision-making authority so their influence is limited. But without them, we'd have little access to influence the process. While I was at MDA I had a few meetings with a group here in Tucson called the "Critical Path Institute" that can also help with FDA regulatory issues and they are very well-connected at FDA. We may be able to enlist their aid as well in taking on exon-skipping.

Ofelia Marin said:
Exactly. Or even save lives next year, or the year after that, or years form now. When you say clinical trials will start in the next "few" years, will not make anyone who knows how many years it takes from the start of a trial to market approval in the US feel better.

We have, in exon skipping, something that can start THIS year w/o safety concerns (since it's already tested in boys in Europe for more than a year now, not to mention the safety profile of morpholinos). What is wrong with this picture and why does this happen when you say that you have a good relationship with the Office of Orphan Products at the FDA? Do they understand that DMD is 100% fatal and that there is a SHORT window of time when an exon skipping treatment (if ever approved) can be therapeutic? Above all, how can they explain to us (parents and DMD patients) why a boy in Europe has the right to be treated before a boy in the US?

It is ridiculous really, we are waiting for approval of a small, 32 patient-12 week trial (AVI/Columbus), not a Phase III trial. I am sorry but, at this point in time, I do not buy it.

I do understand the safety concept, I have a PhD in statistics and I have been involved in clinical trials; I am reading most of the published papers. I understand how complex DMD is and the need for a cocktail of medications to stand a chance to treat it. I've heard the "FDA did many good things" already...why aren't they doing the right and sensible thing now?



cheryl cliff said:
Hi Mindym

I completely agree with your position and feel the same as you. Alexander is going off his feet soon and we know what comes after that. We too are in a hurry to get something to save our son. My question is for Sharon, with death staring us in the face WHY in the world is it impossible to sked a meeting sooner than next fall? Obviously the FDA isn't getting the urgent message that meetings need to be held NOW in order to save lives this year!!

Mindy said:
Cheryl - I totally get that. I really do. But I feel like I'm looking at a 1 1/2 year window here to get something in his body before he possibly won't get the kind of results that I hope for from exon skipping. We all know that it will work better the earlier the boys can get access.

And I'm tired of being patient. I will not be that parent who watches my dying son saying, "Gee - I wish they had just pushed that drug through the approval process one year faster." I swore when he was diagnosed that I would have no regrets, and that doesn't include waiting passively if it seems there is work to be done. But maybe I just need a sedative.

Sharon - thank you very much for the information. I thought that exact meeting you're describing took place already in London last fall. Why on earth is the FDA planning another one that sounds exactly the same one year later? Was nothing accomplished last fall?
I dont think any of us parents with slightly or alot older kids have been patient. We all do what we can. I also dont think any parent with a dmd child has sat back and said, gee if only they would have pushed that drug through faster....Every parent out there is fighting tooth and nail for their child. I think for those of us with older kids, we have gotten our hopes up way way too many times, only to see it not come through. I remember when my son was diagnosed 9yrs ago hearing that a cure would be found in the next 5-10yrs and about alot of the clinical trials then that went nowhere. I read the discussions and the comments that say this year is going to be THE year, etc etc, and I DO have hope, but I also have the past 9yrs where the same thing was said year after year. I no longer look for "the cure" i look for the best life for my son while he is here. If he was younger, it would be different, but you can only get your hopes up so much and so long before you burn out and become negative about it all.....

--Samantha
This topic was the subject of a meeting hold in Europe last year and an FDA representative was there. Pat has all the details, she also posted a blog about it.

Sharon Hesterlee said:
I agree that a meeting in the Fall seems a bit too long to wait, but the topic of that meeting will likely revolve around whether each set of oligos will be treated as a separate drug, not whether or not the AVI trial should move forward now.
Sharon

cheryl cliff said:
Hi Mindym

I completely agree with your position and feel the same as you. Alexander is going off his feet soon and we know what comes after that. We too are in a hurry to get something to save our son. My question is for Sharon, with death staring us in the face WHY in the world is it impossible to sked a meeting sooner than next fall? Obviously the FDA isn't getting the urgent message that meetings need to be held NOW in order to save lives this year!!

Mindy said:
Cheryl - I totally get that. I really do. But I feel like I'm looking at a 1 1/2 year window here to get something in his body before he possibly won't get the kind of results that I hope for from exon skipping. We all know that it will work better the earlier the boys can get access.

And I'm tired of being patient. I will not be that parent who watches my dying son saying, "Gee - I wish they had just pushed that drug through the approval process one year faster." I swore when he was diagnosed that I would have no regrets, and that doesn't include waiting passively if it seems there is work to be done. But maybe I just need a sedative.

Sharon - thank you very much for the information. I thought that exact meeting you're describing took place already in London last fall. Why on earth is the FDA planning another one that sounds exactly the same one year later? Was nothing accomplished last fall?
Sadly there really isn't good coordination between the EMEA and the FDA. Even though the FDA sent a rep, that person may or may not be the decision maker there. It's really hard to get FDA reps at foreign meetings because their travel budgets are so tight. They are horribly understaffed and underfunded--not defending any of the players here, but it helps to figure out what the root of the problem so that we can address it constructively. As much as I like the idea of torches (I know you didn't suggest that but I really did enjoy the mental image) if we burn down the FDA we will still have no way to get drugs approved. I can feel the palpable frustration here and I've already sent a note to Pat about our tyring to engage the C-Path Institute to help.

Ofelia Marin said:
This topic was the subject of a meeting hold in Europe last year and an FDA representative was there. Pat has all the details, she also posted a blog about it.

Sharon Hesterlee said:
I agree that a meeting in the Fall seems a bit too long to wait, but the topic of that meeting will likely revolve around whether each set of oligos will be treated as a separate drug, not whether or not the AVI trial should move forward now.
Sharon

cheryl cliff said:
Hi Mindym

I completely agree with your position and feel the same as you. Alexander is going off his feet soon and we know what comes after that. We too are in a hurry to get something to save our son. My question is for Sharon, with death staring us in the face WHY in the world is it impossible to sked a meeting sooner than next fall? Obviously the FDA isn't getting the urgent message that meetings need to be held NOW in order to save lives this year!!

Mindy said:
Cheryl - I totally get that. I really do. But I feel like I'm looking at a 1 1/2 year window here to get something in his body before he possibly won't get the kind of results that I hope for from exon skipping. We all know that it will work better the earlier the boys can get access.

And I'm tired of being patient. I will not be that parent who watches my dying son saying, "Gee - I wish they had just pushed that drug through the approval process one year faster." I swore when he was diagnosed that I would have no regrets, and that doesn't include waiting passively if it seems there is work to be done. But maybe I just need a sedative.

Sharon - thank you very much for the information. I thought that exact meeting you're describing took place already in London last fall. Why on earth is the FDA planning another one that sounds exactly the same one year later? Was nothing accomplished last fall?
Oh, Samantha, I understand all that and believe me I do not look at a start of a clinical trial as certain way to have THAT drug approved. However, I think that w/o starting a clinical trial there is no way they/researchers/drug comps etc and us learn more about DMD and get closer and closer to an approval. Maybe that drug will not be approved but we/they can definitely learn more from the entire process and use that knowledge to increase chances to eventually find something that works.

I do not think that a cure can be found anytime soon. If you look at all the research done, it is very clear that nothing they are working on at the moment can result in a cure...not even close. I do however believe that a combination of drugs can result in a TREATMENT (look at a combination of exon skipping or Ataluren and myostatin inhibitor for example, several research groups proved that it works a lot better than each drug alone, in animals that is...). When? I do not know. But we are not getting any closer if trials are on hold. I also do not think that 2010, 2011, 2012 will be any different from 2009 (not to mention the years before) in the sense that a treatment can be approved for ALL the boys, BUT we will see more and more clinical trials which means progress. They might be successful or might not, but it is still progress. And it is indubitably significantly more progress than in the last 10 years!

Samantha Dearing said:
I dont think any of us parents with slightly or alot older kids have been patient. We all do what we can. I also dont think any parent with a dmd child has sat back and said, gee if only they would have pushed that drug through faster....Every parent out there is fighting tooth and nail for their child. I think for those of us with older kids, we have gotten our hopes up way way too many times, only to see it not come through. I remember when my son was diagnosed 9yrs ago hearing that a cure would be found in the next 5-10yrs and about alot of the clinical trials then that went nowhere. I read the discussions and the comments that say this year is going to be THE year, etc etc, and I DO have hope, but I also have the past 9yrs where the same thing was said year after year. I no longer look for "the cure" i look for the best life for my son while he is here. If he was younger, it would be different, but you can only get your hopes up so much and so long before you burn out and become negative about it all.....

--Samantha
One more question Sharon,

Would you be able to provide any insight as to why BioMarin isn't conducting Phase I in the US? Are they up against the same dilema with the FDA as AVI? Even with a different chemestry which isn't mutation specific?

Perhaps I should begin buying lots of sweaters in preparation for going over the pond. :)
Hi Cheryl--

I'm not aware of any specific regulatory problems for utrophin upregulation in the U.S. The explanation may be as simple as the fact that the company has European division and the drug was originally inlicensed from a UK biotech company (Summit PLC, formerly VastOx which I always thought of as "BigCow" in my head). I have a long list of companies that I plan to visit over the next few months (just did a site visit at PTC Therapeutics) and Biomarin is on that list. It's one of the few companies where I don't actually know anyone, but plan to remedy that. Don't go over the pond yet!

cheryl cliff said:
One more question Sharon,

Would you be able to provide any insight as to why BioMarin isn't conducting Phase I in the US? Are they up against the same dilema with the FDA as AVI? Even with a different chemestry which isn't mutation specific?

Perhaps I should begin buying lots of sweaters in preparation for going over the pond. :)
Samantha - I'm not saying that parents of older boys are being passive.

I'm saying that I feel like the regulatory authorities are asking us to be passive.

I hope the difference makes sense - we're all standing on the backs of the people that came before us...
Sharon - I guess what I meant when I said that there is work to be done is that we should schedule a conference call between Elizabeth McNeil, who attended the meeting in London, and whoever is planning this upcoming meeting. There is no reason to lose a year. Shoot - I'll do it if you'll give me their names. Dr. McNeil heard the reasonable approach the EMEA is taking to the issue, and should be disseminating that information around the FDA so that people wouldn't even consider a duplicate meeting necessary.
Adding on to what Samantha mentioned we need to be taking care that we as a group are not contributing to the process that focuses on making false claims.

Sharon, since you are so actively participating in this debate I would like to draw your attendtion to the ICE project that made a splash with trying to find a cure by combining exon skipping and stem cells. This project was reported on this website and is also listed on PPMD France website. Last publish said that this Jan 2010 there will be follow up meetings and updates. Jan 23rd came and went and not a whisper on this ICE project. I would expect that we pursue the folks and make them give the new updates. If these folks are not responsive then we should take care and not publish any material from these guys.

I dont know if I am being too hard on this one group by singling them out, but patience is not a virtue I would like to have in this situation.



Samantha Dearing said:
I dont think any of us parents with slightly or alot older kids have been patient. We all do what we can. I also dont think any parent with a dmd child has sat back and said, gee if only they would have pushed that drug through faster....Every parent out there is fighting tooth and nail for their child. I think for those of us with older kids, we have gotten our hopes up way way too many times, only to see it not come through. I remember when my son was diagnosed 9yrs ago hearing that a cure would be found in the next 5-10yrs and about alot of the clinical trials then that went nowhere. I read the discussions and the comments that say this year is going to be THE year, etc etc, and I DO have hope, but I also have the past 9yrs where the same thing was said year after year. I no longer look for "the cure" i look for the best life for my son while he is here. If he was younger, it would be different, but you can only get your hopes up so much and so long before you burn out and become negative about it all.....

--Samantha

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