ATALUREN - confused about the information given from PTC Therapeutics and Genzyme


Hi Sharon and Pat

or anyone else who can help


Can someone PLEASE help me understand the information given from PTC Therapeutics and Genzyme, regards to Ataluren. Our son can use Ataluren, and he is about to stop walking. He didn’t participate in the
previous clinical trials, because the enrollment was closed before our son
could enter the trial. I know there are many other boys ”out there” in the same

I am asking for several other parents coming from Norway,but also parents coming from other contries.


First we had this article from the Annual Meeting of the American Academy of Neurology, published

April 13th. This article didn’t say anything that this is going to be a follow-on clinical study of Ataluren, so I thought ohhhhh finally Ataluren will be on the market in the USA (if approved by the FDA):



AAN 2011: Ataluren Reduces Decline in Ambulation in Duchenne Muscular Dystrophy

Based on these results, PTC Therapeutics, the company that developed ataluren, is planning to seek approval for its use in DMD from the United States Food and Drug Administration. Because of
the mechanism by which the drug overcomes the effects of the mutation, it would
be appropriate for only about 13% of DMD patients, according to study presenter
Ted Abresch, Research Associate in Neuromuscular Disease at the University of
California at Davis.


The whole article published April 13th 2011


Then today, this article was publised by Genzyme. They are talking about a follow-on open label clinical study for previous trial participants, in Europe.


Ataluren update from Genzyme

Follow-on open label clinical study announced for previous trial participants

As part of our continuing assessment, Genzyme plans to initiate a follow-on clinical study of ataluren in nmDBMD patients who previously participated in the clinical trials in Europe, Israel and Australia.
All patients who have previously participated in the clinical trials with
ataluren in nmDBMD, irrespective of their current clinical status, will be
eligible to participate.

We believe that this clinical study will allow for the collection of additional information on ataluren in nmDBMD while providing access to ataluren to all patients who have been involved in earlier clinical trials.
Currently we are working to develop the timelines and design for this clinical
study and we plan to update the community, with these additional details in the
very near future. We are reaching out to the original trial investigators to
make them aware of this new development and they may be in touch with eligible
families directly as well.

The whole article posted May 2nd 2011:


When/if Ataluren is approved by the FDA in the USA, is this an approval for all Stop-codon-boys in the USA ? Also those who didn’t participate in the previous clinical trials ?

When/if Ataluren is approvad by the European regulatory authorities, is this an approval for all Stop-codon-boys in Europe, also those who didn’t participate in the previous clinical trials ?


Can someone please help.



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I would also be very inerested to hear if anyone from PPMD knows about this article David posted. 


This news is also presented on
BeritSofie said:

I would also be very inerested to hear if anyone from PPMD knows about this article David posted. 


I think this is more analysis of the Phase 2B study - it was 48 weeks, about the same number of boys enrolled and was a double blind study.  I believe this is the analysis of the secondary endpoints - not the results of the 6mwt which was the primary endpoint. 


PTC will be presenting during our annual conference in June.  They will be discussing 'next steps'.    As suggested in the article, they are planning for the follow-on study  for individuals who have previously participated in trials.

  They are working with regulatory agencies, but ataluren is not currently approved in Europe or the US. 

You are correct to say that if a drug for DMD would be approved in Europe or the US, the drug would then be approved for all DMD boys who fit the criteria (for instance, stop codon, skipping of a particular exon, or for all if the approach is general such as myostatin, antifibrotics, etc)

PTC is working really hard on their 'next steps' and we all expect to hear specifics in the next few weeks.  



Thank you for your reply, Pat. 

What I really don't understand, is that after reading this article claiming some positive effects, how can they continue to do a follow-on study only for the boys who participated in previous trials ?  Boys who couldn't participate in the trials are now getting older and weaker - while the drug is given to the boys "inside the trials". Is it possible for Parent Project to influence in some way ? Why can't they(PTC)  expand the trial to all boys with stop codon ? 

I only hope that after wasting already two years since the trials were stopped because of a 30 centimeter (11inch) difference in the 6MWT, this time around the FDA and all involved speed the whole approval process up!. I don't know what else it takes to convince these guys: at the lower dose, the drug is harmless and it certainly slows down the progress of the disease in a significant way; maybe it even restores some strength in the boys' muscles.  

I thought that the follow on study started long ago, soon after the trial ended? I am confused now. What does "planning" mean? 2 years later they are still planning? Is this reffering to the other countries?

I am baffled as to why PTC can't file for subpart H for ataluren. Pat - do you know the answer to that question?

Agree Bernando

The lower dose is harmless, and it slows down the progress - maybe even restores some strength.

And here we are, having a boy lossing strength each day - can barely walk anymore. I have said it before, and I say it again:

This is UNETHICAL.  


It is absolutely unethical to put another boy on an ataluren placebo when it seems to meet all of the requirements for subpart H approval. The drug gets conditional approval, everyone gets on it and participates in a confirmatory study, the FDA gets additional data...

Why is this so hard? It seems very straightforward to me...


Berit - can you contact PTC and ask why they have not filed for subpart H based on this data?


This is incredibly frustrating I know.  Like all of you, we want/need drugs approved in DMD.  Keep in mind, ataluren was the first industry sponsored trial.   As you know the 6mwt was identified as the primary outcome measure.  At that time, we had no natural history studies and were unable to correlated other measures (north star, timed function testing, etc) to the 6 mwt.

The pivotal trial involved two doses (high and low) and placebo and included boys 5 years and over who were ambulatory.   The trial was based on the 6mwt as the primary endpoint and the belief that ataluren would demonstrate a 30m change in the 6mwt.

What we now know about the 6mwt.  We now know that it correlates with timed function testing (McDonald).  We know that boys who walk <250m are likely to go off their feet within 48 weeks.  We also know that boys who walk >350 m. are likely to be stable throughout the duration of the trial.   As some of you have learned, more recent studies exclude boys outside certain parameters of the 6mwt.

You all may recall that the ataluren trial was terminated because interim analysis suggested the high dose was not effective. (keep in mind, the trial was based on the high dose).  With additional analysis, the low dose was suggested to have an effect.   

Keep in mind, in the process of drug development, the sponsor has to describe the study, what the study is suggested to achieve (in this case a 30m difference in the 6mwt) and on what dose before the study gets the 'go ahead' from regulatory authorities.  . 

ALL of this is known and has been shared in private and public forums.

.   To answer your question Ofelia.  PTC initiated an access program in the US for boys who had participated in trials.   Keep in mind, at the time this access program was initiated, Genzyme was responsible for countries outside US and Canada.  Because the relationship with Genzyme is no longer in place, PTC has recently initiated the program for boys in Europe and Israel who have participated in the trial.

Berit,  You are right, ataluren is safe and well tolerated. I'm thankful that you believe it has demonstrated efficacy on low dose.    As you know there are statistical requirements that must be met  in order to demonstrate efficacy.  to repeat:  In the pivotal study, high and low dose were tested.  As you know. the trial was terminated when the high dose failed to show efficacy.   Clearly after significant analysis of the data, it appears that the low dose had an effect, demonstrated a trend toward benefit.    As you might imagine, another study needs to be conducted to determine if the low dose meets statistical relevance and to learn if the low dose (10/10/20) is the 'best dose'.    

I'm sure, by now you have a headache.   In our heart of hearts, we think ataluren provides benefit.  At the same time, FDA wants to insure drugs are both safe and effective.  We can agree that they are 'risk adverse' and need to learn more about DMD, how difficult it is to tease out benefit, how subsets of boys may respond differently -better or worse.   This is exactly why we met with FDA and have ongoing meetings planned.  It is 'tricky' as Dr. Temple said during our meeting.     Drugs/biologics have to reach statistical relevance in order to prove that a certain drug or biologic works and that there is less than 5% chance (p value.  p=0.05) that whatever we are seeing did not happen  by chance, fluck, luck.   That the effect is real.

Mindy,  while you have the sense that ataluren meets the requirements for subpart H, it is not be the case.  Clearly the drug is safe and well tolerated.  I also realize this seems quite straightforward to all of us who believe the drug provides benefit on low dose.   That said, Regulatory Authorities need to agree and at this moment, ataluren has not been approved in the US or Europe. 

We recently met with the Neurology division of FDA.  Dr. Temple said that there is NO conditional approval in the US.  Rather, accelerated approval is possible, based on certain requirements and an agreed upon follow-on study.   At this moment, ataluren has not met the requirements for accelerated approval.

PTC is working very hard on regulatory issues in the US and Europe.   Dr. Jay Barth will be presenting during PPMD's annual meeting.   I am certain he will be able to answer most if not all of your questions.


Jeez... :(

It's a nightmare to even think about exon skipping after reading all this. At this speed, 100 years from now there might be a treatment approved for Duchenne. I wonder how much more clear we can be that our boys are dying, they are dying NOW. They do not have time to wait for this. How can we make these people get it? The rules need to be relaxed otherwise we'll just continue to watch these boys passing away while looking at drugs that can slow their progression go from study to study to study.

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