Last night I watched the recording of the Ataluren webinar, held on January 17, 2013. Excuse me for not sounding particularly upbeat about it. I know that PTC and everyone at PPMD are doing as best they can in order to finally get approval for this very successful drug, but I could not avoid a sense of deep frustration and anger, which was triggered about mid-way into the webinar recording, when in one of the slides it became clear for everyone to see that the primary endpoint in the Phase 2B trial that was stupidly cancelled three years ago (a Delta of 30 meters in the 6 minute walk test) had not only been ACHIEVED, but that it had actually been SURPASSED.

While the preliminary reports that led to the cancellation of the trial in March 2010 talked about a Delta of "only" 29.7 meters in the 6MWT between the placebo cohort and the boys who had been on low dose Ataluren (a shortfall of just 1% that for anyone possessing common sense would habe been touted as a resounding success), it now turns out (THREE YEARS LATER!!!), that the Delta was actually 31.3 meters. This means that rather than a 1% shortfall in the expected results of this particular primary endpoint, the boys on low dose Ataluren had actually beaten the goal.

I am simply outraged to learn that at least five precious years have been wasted because of the defective funtioning of the brains of those who gave the order to stop that 2010 trial. I say five years because, as the webinar informs us, it won't be until mid 2014 that PTC will be able to recruit the 220 boys that are needed for the Phase III Trial. Add to that the year it takes to conduct the trial and you are already in 2015. By then, many boys with DMD who could be benefitting right now from Ataluren will be dead.

At the end of 2015 we will attend another webinar where they will tell us that indeed the earlier results were correct, and that the low dose regimen shows remarkable attenuating results. In short: the trials were stopped in March 2010 because of the actions of stupid and incompetent people. Is there anybody being held responsible for this inexcusable waste of time?

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Thank you very much Michael for your comment. I gather that your son was fortunate enough to be part of the trials, and that he is now allowed to continue taking Ataluren because of that. I am really happy that at least some boys are receiving this truly successful drug and that their families are able to experience now what the rest of us will only see with our eyes in 5 years (optimistic estimate), if our boys are still around. The narrow-mindedness of the people responsible for aborting the trials early in 2010 because of a ludicrous defficiency of just 1% in the 6MWT still is beyond my comprehension, especially now that we learn that the low dose group actually EXCEEDED the goal. It should also be beyond the comprehension of anyone possessing rudimentary reasoning skills, but apparently that is not the case. They tell me that before sitting down some day to maybe consider a hypothetical acceleration of the approval process, a poll of some sort would have to be conducted (in the US only) to see if parents of boys eligible for treatment with Ataluren are willing to take the (non-existing) risk of allowing their sons to receive the (patently successful) drug. Again, thank you very much for stepping up and telling us about your very concrete experience.

Michael Piacentino said:

Ouch,

Didn't see the Webinar; and most certainly personally frustrated with the protocol,process,procedures of  PTC-124, but someday someone will admit it actually works and the FOUR (4) biopsies my son endured will prove worthwhile. Meanwhile, back at the ranch here, we trudge on, advocating and arguing for the justification and value proposition of Ataluren.  At least after 7 years it has a name, of sorts.  It mostly works, it's just unfortunate for our son that the process of getting it authorized is so painfully slow. My son is walking albeit not as much as I'd like to see but light years beyond anyone else his age who has not had the benefits of the drug cocktail we serve up everyday of which PTC-124 is an integral part.   Yep...

  

Hi Michael, how long is your son on low dose ataluren? 
 
Michael Piacentino said:

Ouch,

Didn't see the Webinar; and most certainly personally frustrated with the protocol,process,procedures of  PTC-124, but someday someone will admit it actually works and the FOUR (4) biopsies my son endured will prove worthwhile. Meanwhile, back at the ranch here, we trudge on, advocating and arguing for the justification and value proposition of Ataluren.  At least after 7 years it has a name, of sorts.  It mostly works, it's just unfortunate for our son that the process of getting it authorized is so painfully slow. My son is walking albeit not as much as I'd like to see but light years beyond anyone else his age who has not had the benefits of the drug cocktail we serve up everyday of which PTC-124 is an integral part.   Yep...

  

Hi,

Our son started when he was 15 in the original trial 9/2008, then following that was in the next parallel trial ( there were so many variations on that theme) I guess he's been on the low dose for a couple of years now. His biggest plus has been Deflazacort. Were it not for that, I don't think he would have been doing as well as he was to get into the trial. He's now 19 and walking a bit, but at 15 when he was entered into the original trial,he had no problem doing the 6 min. walk test, so I'm a large proponent of deflazacort. Ataluren is nice to have, but I cannot say how much of a difference it's made. Certainly not in his concentration at college.

Regards,

Mike

Totally share your frustration. Having a son with Stop Codon myself, and was ready to go to the UK to participate in the clinical trial. We had ordered air tickets, and very, very eager. Just a few days before our travel, message from PTC - stop enrolling. Will not use too much time on this, but because our son couldn't participate in this trial we are excluded from receiving the drug (extension study). 

My question to Sharon and/or Pat:

several kids worldwide need this medication. We CANNOT wait until approval. Can you please guide us:

1. Should we try to get the drug by sending an application to the FDA for expanded access/compassionate us ?

After watching the FDA's webinar on  accelerated approval, I think its worth trying. I also suspect that the FDA will give approval. But then what ? If I understand this correctly, its up to PTC if they want to give access of the drug outside the trial. 

2. Is it possible for PPMD to help pushing PTC if kids are having approval from the FDA ? (didn't PPMD cover some of the costs of these trials?) 

Its just heartbreaking to watch the clock as Bernando stated, and we know this drug could help. What should we do ?

Berit

Berit--you are right that the decision will lie with the company.  They can't sell the drug until they have FDA approval so they can only make it available for free and I doubt they have the money to provide the drug for free to everyone who would benefit.  We did provide some funding to the company to help them cover the costs of the regulatory process for making the drug available in the continuing access program for the boys who particpated in the original studies, but we aren't covering the costs of providing the drug itself (it was actually MDA that provided the most funding to support the development of Ataluren).  It is heartbreaking and there's no straightforward solution.   It looks like there's a chance that the drug might receive approval in Europe if the phase III in the US proceeds on schedule--at least the company has applied for that approval and the European Medical Agency has agreed to review the application.  But a key part of that application was the promise that the phase III would proceed in the US and that more data would evenutally be available  So I'm not entirely sure yet what an approval in Europe would do for us in the US, but my guess is that there would be ways to bring the drug into the country.

 

Sharon

Thank you for your reply, Sharon.  

Is it possible to influence on the application to the EMA ? Guess they are having the same role as FDA in the US. Thinking here of benefit contra risks, data collected from the low dose.  If its possible to influence on the FDA's desicion, it most be possible to do the same with EMA ?

When do you think we will have an answer to this application ? 

Berit 

 

Hi Berit--I don't know the time line but am happy to ask PTC Therapeutics if they know it.  In theory we might be able to persuade the EMA.  Pat and I just spent a week in Europe meeting with various European funding groups (UPPMD, Duchenne Research Fund, AFM, Action Duchenne and several private funders) to talk about these issues.  I know Pat has been invited back to go to the Houses of Parliamint in the UK at some point to advocate for funding and smoother regulatory approvals.  We are also thinking about how to "export" our risk/benefit survey to Europe--it will require some adaptation and we would partner with one of our sister organizations there, but risk/benefit data might be useful in pushing the EMA toward a positive decision.  Sharon

Sharon, please ask PTC for us. 

Will be looking forward to hear back from you again. 

To other Stop-Codon-Parents here: Did you see the positive respons from Sharon ? In theory its possible to try to persuade EMA (The European Medical Agency) to give approval of Ataluren. The drug will then be approved earlier in Europe, and this can benefit all of us. First, and most important goal must be to GET APPROVAL FAST - and then we will sort out how kids outside EU can get the drug. THIS IS IMPORTANT INFORMATION. 

Please, please Sharon and Pat - try to work as hard as possible to persuade the European Medical Agency. We need this drug NOW !!!!! 

Our son got stop-codon. We live in Vietnam where is far from either Europe and USA. My son cannot attend the trial and we do not know how and when we can connect with. Yes, we need this drug NOW.

Thank you very much Berit and Sharon. I certainly hope that the Europeans act upon PTC's application as soon as possible. I am concerned though, when Sharon says "It looks like there's a chance that the drug might receive approval in Europe if the phase III in the US proceeds on schedule--at least the company has applied for that approval and the European Medical Agency has agreed to review the application. My understanding from the Webinar is that it will take the whole of 2013 and perhaps part of 2014 for PTC to recruit the 220 candidates they need for the Phase III trial, and then the trial itself will last one more year, so I am not sure if the European approval process will actually be speedier than its counterpart in the US.

I fully share your opinions Berit, and also what Trinh Nguyen said in his post. 

If there is an effective way to lobby the EMA from my corner of the world please let me know.



BeritSofie said:

Sharon, please ask PTC for us. 

Will be looking forward to hear back from you again. 

To other Stop-Codon-Parents here: Did you see the positive respons from Sharon ? In theory its possible to try to persuade EMA (The European Medical Agency) to give approval of Ataluren. The drug will then be approved earlier in Europe, and this can benefit all of us. First, and most important goal must be to GET APPROVAL FAST - and then we will sort out how kids outside EU can get the drug. THIS IS IMPORTANT INFORMATION. 

Please, please Sharon and Pat - try to work as hard as possible to persuade the European Medical Agency. We need this drug NOW !!!!! 

Hi Bernardo, and one more question to Sharon

Share you fear for the timeline, Bernardo. Not sure how to lobby the EMA, but Sharon mentioned earlier that having the parents voice up front when it comes to what we are willing to risk contra benefit could be the right way to go ???? I guess this is one of the points Sharon and Pat will discuss if they meet with the EMA. 

One more question to Sharon/Pat:  Thinking of the timeline here, is it now possible to try to apply the FDA for compassionate use or expanded access ?

Berit

Hi Berit--

 

We are in the process of finalizing a white paper now that pushes the FDA on issues of flexibility in trial design and faster approvals for rare disease--it compares all the new proactive legislation with what they are actually doing.  We could do something similar for the EMA, although the EMA has actually been much more flexible in their standards for rare disease already. 

As for expanded access, I think that application has to come from the drug sponsor.

 

Sharon

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