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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It's been a long time since we all exchanged the above comments. In the meantime, a rather incompehensible piece of news came recently from PTC. The company announced that a crucial committee of the EMA has issued a negative opinion on PTC's own application for conditional approval of Ataluren for DMD. The most difficult part to understand of PTCs press release is when they say that the negative opinion of the Committee (a sure sign that the EMA will not issue a conditional approval), was consistent with PTC's own advise on the matter!!. 

They now say that the Phase III trial is essential before getting a green light. This begs the question of why in the world did they apply for conditional approval in the first place?

At this point I think I do not understand anything at all concerning Ataluren, after eleven years of placing my hopes in something that I still consider the ONLY drug that proved to be susccessful in slowing down DMD's progress in boys with a nonsense mutation.

By the way: is there any video or transcript of the February 5, 2014 webinar?

Here is the link to PTC's press release.

http://ir.ptcbio.com/releasedetail.cfm?ReleaseID=820977

Regardless of what the facts are and why certain decisions get made in these trials, I can feel it coming that twenty years from now, people will look back on this time as the tumultuous and heartbreaking time DMD drugs went through in their early days. I know there is a lot involved in conducting a clinical trial, but man alive it seems to take a shocking amount of time to complete one, especially with all of the roadblocks that seem to consistently pop up at every turn. Thank you PPMD, for putting so much time and effort into trying to speed this process up. Hopefully one day we won't have to wait so long for something that works to get approved.

It would help a lot if PTC were able to clarify why they applied for conditional approval in Europe (and made many encouraging announcements about it back then) and then changed their mind and advised that Committee of the EMA to say no.

Me too, I was so frustrated with the news that the Committee issued a negative opinion. For me another question arise, PTC is to ask the Committee for reexamination. It is not coherent with all the points you/they stated. Maybe they want to enroll participants for the ACT trail before conditional approval may be granted.

Bernardo--here is the recording of the most recent Webinar: 

http://community.parentprojectmd.org/events/act-dmd-update-with-ptc-webinar

I don't think PTC Therapeutics ever advised the EMA to turn down their application for accelerated approval--they wanted the drug approved in Europe if possible.  I believe that they will appeal the decision.

Sharon
 
Bernardo A. Iriberri said:

It's been a long time since we all exchanged the above comments. In the meantime, a rather incompehensible piece of news came recently from PTC. The company announced that a crucial committee of the EMA has issued a negative opinion on PTC's own application for conditional approval of Ataluren for DMD. The most difficult part to understand of PTCs press release is when they say that the negative opinion of the Committee (a sure sign that the EMA will not issue a conditional approval), was consistent with PTC's own advise on the matter!!. 

They now say that the Phase III trial is essential before getting a green light. This begs the question of why in the world did they apply for conditional approval in the first place?

At this point I think I do not understand anything at all concerning Ataluren, after eleven years of placing my hopes in something that I still consider the ONLY drug that proved to be susccessful in slowing down DMD's progress in boys with a nonsense mutation.

By the way: is there any video or transcript of the February 5, 2014 webinar?

Here is the link to PTC's press release.

http://ir.ptcbio.com/releasedetail.cfm?ReleaseID=820977

Bernardo -  I have some mixed emotions on this. My son is now 20.

When I first heard about this drug in research/development and prospects in 2000,  I was sure this was a viable drug by 2004. Now 14 years later, PTC has compiled significant data, to show the positive delaying of DMD progression.

I don't understand why they don't present all their data in an overall presentation, to acknowledge the drugs safety and efficacy in delaying the effects of DMD. 

??? What is going on at PTC ???

Thank you Peter and Michael for your comments. 

Thank you very much Sharon for the link to the webinar's recording and for being responsive and kind to this community's frustrations and worries .

PTC says in its press release that 

"... the CHMP of the EMA has adopted a negative opinion on the Company's marketing authorization application (MAA) for conditional approval of ataluren for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD). The response from the CHMP is consistent with the Company's previous guidance concerning the substantial risks regarding conditional EMA approval and underscores the importance of PTC's work in completing the ongoing confirmatory Phase 3 clinical trial".

I would ask them what "substantial risks" are they talking about when the drug has been known to be safe for about ten years, after the Phase I trial was completed?, And again: why did they apply for MAA in the first place, if they consider that conditional approval entails substantial risks?.

They do say further on in their release that "PTC intends to request a re-examination of the CHMP opinion with a final outcome expected in the second quarter of 2014, when the confirmatory study is expected to be more fully enrolled". 

I don't see how the Committeee could revert its negative opinion simply because an XX number of boys are enrolled in the Phase III trial. In PTC's own words, they will have to wait until the Phase III study is over. That is what they told the EMA.

Bernardo, I think they mean substantial risk from an investment standpoint, not due to any issues with the drug.  Because they are a public company they have to be pretty guarded about how "forward looking" their comments are--I think they probably used a lot of hedge language about their chances of getting conditional approval and are now citing it as if they knew it was a long shot.  But I also think the environment has changed since they first filed the application--the failure of drisapersen in phase III has put a bit of a damper on everyone's way of thinking, unfortunately, and may have influenced things. 

Sharon

Sharon, How do you think is it a good idea to write a letter to EMA/CHMP to try to persuade them to admit conditional acceptance to Ataluren when reexamining the data from PTC.

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