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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I was also surrprised with 31,3m. So the primary endpoint of the study was achieved in 2010?

Yes. That is what the revised results of the 2010 trials show, according to PTC. Why on earth it took them three years to announce the new, revised figure of 31.3 meters is beyond my comprehension, just like all the other chain of unbelievable events that led to the unwarranted cancellation of the Phase 2 B trial and the subsequent loss of more than five years in a life-threatening situation like this.

I simply do not understand why is it not possible for PTC, supported by PPMD, the MDA and other concerned parties to simply demand approval NOW for a drug that has PROVEN beyond any doubt to be beneficial for boys having a stop codon mutation.

Anyone from PPMD care to comment? 

Hi Bernardo--

Just to clarify, Ataluren really didn't meet it's original endpoint...the results they showed at the meeting involved subtracting the high dose data and redoing the statistical analysis.  The FDA doesn't generally allow you to re-evaluate the statistics after the fact because there is a risk that you can keep re-evaluating and be more more likely to get a positive result by chance.  I think, sometimes, you can make a compelling argument that it really makes more sense to evaluate the statistic in a way other than originally proposed and that's the argument PTC made to the FDA but it sounds like they were encouraged to just do the phase III trial. 

One way we can try to speed things up is getting data to the FDA on the risks that parents are willing to accept--that will lay the groundworking for getting the FDA to be less conservative in its decisions.  We are launching a risk/benefit survey in the US (in beta testing now) that will help get us that data. I understand that this doesn't change the immediate time line and I know what that means for progression but it's what we can do right now that would be constructive.



Thank you very much Sharon, but I was under the impression that when they showed the 29.7 meter figure in 2010, that was already exclusively the low dose data, and now they come up with a revised figure of 31.3 meters that doesn' t look to be affected in any way by any prior information on the high dose group.The high dose group always showed no difference with the placebo group and they have not revised that conclusion. Moreover, when they now subtract the 5 and 6 year old boys who took part of the trial and incorporate data only from boys over 7years old (low dose), the Delta is above 40 meters!

I have been eagerly following all the news concerning PTC124 since the potential drug was first announced ten years ago, when my son was still ambulatory. To me it continues to be impossible to understand that they are being forced to conduct a Phase III study with such robust data from the Phase II B Study.

My point is that already the 29.7 meter difference was a great success for anybody using common sense, knowing (as they know) that this horrible disease is killing many boys every day. A "shortfall" of 1% should have been counted as within the margins of statistical error. It should have prompted the regulators to approve the drug, rather than to call off the trials in a hurry and sounding ridiculous alarms. 

For my son Hernán (now 22), who stopped walking six years ago and now is rapidly losing the little autonomy he still retains, Ataluren is THE ONLY available treatment that could slow down the progression of his illness. All of the other research avenues being discussed in this and other fora are light years away compared with Ataluren, and it is just infuriating to see that the FDA fails to see such an abvious fact.

As for the risk-benefit survey, considering that the Phase I and Phase II Trials years ago conclusively showed no safety concerns at all, I for one would vote hands down for a green light on Ataluren, even though I still have no idea how much this drug could cost in Argentina or in the US. Since I live in Argentina I assume I won't be able to take part in the survey anyway. Please correct me if I am wrong about this.

Best regards


It doesn't benefit our community to refer to the people working to save our boys' lives as "defective", "stupid", or "incompetent".  They want the drug to be approved nearly as badly as we do.  Their jobs and livelihoods depend on it. 

It's easy to take potshots, with the benefit of hindsight, and without all the facts.   



The order to cancel the 2010 trials was not issued by PTC or PPMD, whose staff are certainly working to save our boys' lives. I was referring to the STUPID and INCOMPETENT people who forced the cancellation purely because the primary endpoint had "failed" by 1%. And I am not speaking with the benefit of hindsight. I expressed my outrage as soon as the cancellation was announced, because it was evident in March 2010 that the Trial was a resounding success for the low dose group given the "nearly" 30 meter difference in the loss of walking ability between them and the placebo cohort. It was evident then, in March 2010 that the FDA (or whoever was responsible for pulling the plug) were acting in a rush and illogically. Three years later we receive confirmation that the decision to stop the trial was  a tremendous mistake, as we now learn that not only there was no failure at all in the 6MWT but that the low dose boys actually surpassed the goal by 1.3 meter. This only reinforces my initial perception, as the correct conclusion about the success of the Phase 2 B trial was there for anyone to see three years ago. I am sorry but I cannot draw any positive conclusion about this major blunder, and I cannot take comfort in the thought that by the end of 2015 we will have an announcement confirming the success of a Phase III Trial, and maybe by 2016 or 2017 PTC will be able to market the drug. 

The FDA didn't pull the plug--it was a recommendation from the Data Safety Monitoring Committee for the trial and companies generally follow the DSMB recommendations.  The DSMB felt that it was unethical to continue treatment with an experimental drug that showed no benefit in any parameter measured based on the original endpoints and statistical design of the trial.  I think for that particular decision a more thoughtful risk/benefit analysis would have been useful.  That's why we want data to back up what we think we all know about the community's willingness to accept risk.  And you are correct that the risk/benefit survey we are beta testing will be conducted in the US.  We are considering follow-on studies that will look at how physicians view risk/benefit and how the boys/men themselves view the topic.  We may collaborate with colleagues in Europe and South America to conduct similar studies.  This all sounds a bit esoteric when you are watching the clock, but the one thing that the FDA responds to is data...anything else you tell them is hard for them to process.  So that's what we are going to give them, in a very rigorous study.



Absolutely tragic. 3 YEARS!

This community really has to run a study to prove we are willing to take risk?? What a waste of time and money.

I am sorry but I agree completely with David. There is no risk and we all know it. The few discomforts and invonveniences that were reported during the trial showed no connection with the drug and the percentage of cases involving those minor inconveniences were identical as those showed in the placebo group. To me it was certainly unethical for the Committee to stop that trial abruptly and to send alarming signals in the face of aboslutely positive and proven results showing a significant clinical benefit for the low dose regimen. How can you say that the drug "showed no benefit in any parameter measured based on the original endpoints", when the lowe dose group came just 1% short of the desired goal? Unless we are all robots, a shortfall of 30 cms out of an expected Delta of 30 meters should have merited a continuation of the trial since there were no side effects at all. What is unethical is to put roadblocks in the way of approval of the ONLY drug that is now and here capable of slowing down the progression of DMD in a significant way, albeit only for those (like my son) who have a stop codon mutation. I'd better stop watching the clock.

Hi Bernardo--to be clear, I didn't say that I agreed with the DSMB decision!



Yes I know Sharon. Thank you.


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...


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