Yesterday was really difficult.

In 1999 our Scientific Director Lee Sweeney published an article on Gentamycin and while that was good news, we knew Gentamycin could not be a lifelong therapy. Then PTC marched into our lives, committing time, talent, and millions of dollars. They paved a road where none had been before. They became friends, invested in our community and our sons.

Over the years, we watched as the words premature stop and PTC124 nearly became household words. We found ourselves hanging our heart on the concept of the first treatment for Duchenne, if only for a subset, knowing that we would do whatever it takes to expand our horizons until every boy had a treatment. PTC developed and executed the first pivotal study of a New Chemical Entity (NCE) in Duchenne.

This is a huge step in and of itself, recruitment completed two months ahead of schedule. Parents/families, physicians, industry all coming together from around the world. Duchenne was studied in a systematic way and more thoroughly than ever before.

The outcome we have received is devastating and the news yesterday threw all of us over the edge. This blow knocked the breath out of all of us and at least for a moment, some of the wind out of our sails. PTC will further analyze the data and we will learn more about the results and the trial.

I’m still hopeful we will see some light and with that, a path forward. Regardless, we are still believers in our sons, in our community, and in PTC.. There will be treatments for Duchenne and we will find them. That is certain. PTC has been building the road and will continue. They are not changing their commitment to our sons. They are acting in our best interests and will continue to stay focused on the road forward.

I just wish the road was a bit easier and without so many damn boulders.

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Comment by Michael on March 11, 2010 at 11:03pm
This research is like going prospecting, that's why we don't call it finding. Even on the digs you can get skunked. There are bushels of data from this trial; and I figure they just made their first sifts through all the data. Lets give PTC a while to grind through the study data.
Watching how the drug effected my son, I know they can dig out lots of good nuggets if they use the right data-mining queries to correlate data. It just takes time when you have so many variables. My son is 16 so I don't like waiting either, but what choices do we have; Besides it's March, it was going to be a trashy time anyway.
Comment by damien lynch on March 8, 2010 at 3:24pm
The news on the Ataluren Trial is disapointing, but you have to commend the company for coming out with this information on the 6min walk test. It's interesting to see that there is no statistical significance, but was there any practical significant improvement for anyone on the trial? Also, the project is not gone.. only suspended...lets wait and see......
Comment by Jonathan on March 6, 2010 at 7:33pm
I understand the dissapointment and the confusion relating to the 6MWT, but I think the test has been mis-understood. The data for the test has compared the results from the boys on high dose against those on the placebo, this is important to remember as the placebo is the baseline for this study. If a boys results are compared blindly then it can be difficult to determine how much improvement or stabilisation has actually occured. When it is compared to a boy who was on a placebo then it will become obvious. I would say that for them to stop the trial like this there must have been very little difference in results between the groups. It is disheartening, but Im sure they will release the rest of the data once it has been analysed. We just have to keep looking forward and encourage these companies to keep on trying.

Comment by Pat Furlong on March 6, 2010 at 8:19am
Ofelia, there is a great deal published on read thru. and in humans, we do not have the % dystrophin and relationship to benefit. We have some guess based on mdx and dog data as you know.
Dogs were not done because they do not have a stop. And this is not over yet. Subanalysis is underway, so let's wait and see.
Exon skipping is a different story all together. its been around for 20 years and in the last 10 investigated for dmd. Trials are underway and in development. My guess is that preliminary results will be out relatively soon or released at the WMS meeting in summer. Registration trials are being planned.
Comment by Ofelia Marin on March 5, 2010 at 9:07pm
Can we look at data in large animals, dogs, monkeys to see the relationship b/w % dystrophin and function/improvement? I am assuming Ataluren was not tested in a large animal, was it? Did PTC show any other data besides the early work in mice -- I looked at this only briefly before; it looks to me that with exon skipping more data is obtained and presented.

Comment by Pat Furlong on March 5, 2010 at 2:29pm
Hello again,
1. Here's what you have to keep in mind. There is NO natural history on boys taking steroids. Natural history studies are in place now, but they do not have long term data.
2. There is NO established relationship between the % of Dystrophin and function. PTC was hoping to correlate % dystrophin with 6MWT.

Also, the 6MWT is not yet predictive of ambulation..we do not have enough longitudinal history with that measure or natural history. This outcome was chosen because regulatory agencies were familiar and accepted this as a primary outcome in other indications. Keep in mind the regulatory agencies want to see benefit in terms of improved quality of life.

3. I agree with you, steady state is improvement in degenerative disease. And you are right, we do not know if it is reliable in 5+boys. In DMD it is especially difficult because of the 'golden years' - the time period that boys with Duchenne improve over time with or without steroids and/or supplements. For some the 'golden years' are guesstimated as 4-7 years, but steroids have expanded this parameter as well.

4. There is a predictive measure in the timed functional testing. Predictive in terms of time to loss of ambulation (not of a specific drug effect). In the 10m walk, when the 10m was above 12 sec, and moved to below 12 sec, they have increased ambulation by almost 2 years... that test is predictive in DMD.

None of this is easy. We are going to continue to press for answers and for a path forward.
Warm regards,
Comment by Ofelia Marin on March 5, 2010 at 1:37pm
Oh, this CC left me speechless and that doesn't happen too often. :) I really thought that they looked carefully at more data in addition to the 6MWT before they stopped the trial. I have only one question left. How was the 6MWT validated as a reliable measure for DMD trials with 5+ year old boys? I am in this DMD world for only 2 years and I can easily find several confounding variables against this. Not to mention the fact that lack of decline/slower decline in DMD would be a dream for all of us.

Obviously, if there is a clear improvement it can easily be seen in the 6MWT and the FDA will buy this in a minute, but is this what we are looking for today, when the steroids are the only approved medication for DMD?
Comment by Bernardo A. Iriberri on March 5, 2010 at 12:57pm
Since thist is my first participation and the conference call is already in progress, I just wanted to say that I agree 100% with what Ofelia and Dalia are saying. Speed cannot be the sole or paramount measure to kill this trial. However, I still remember that when PTC announced and published the preliminary results from Phase 2a, the amount of distrophin in muscles was rather low. Nevertheless I had placed nearly all of my hopes on PTC124 since I discovered it existed 7 years ago. I even first alerted my son's doctor about it. Even though he is a first class specialist here in Argentina at that early stage he didn't know about PTC. My 19- year-old son has a stop codon mutation and you can imagine how important this little light of hope was for our family. I will read or listen to the recording of today's call. Now I guess we have to look at BioMarin and their BM195 trials, but it's going to take a long time. It's good to share these feelings with other parents. Bernardo

Comment by Pat Furlong on March 5, 2010 at 12:50pm
I hope you found the call useful. Please continue to send questions. We will see that they are answered. Please know we are here for all of you and will do whatever it takes to get answers and to accelerate treatments and cure.
Comment by Debbie Dupree on March 5, 2010 at 12:49pm
I just wanted to send a note of thanks to everyone at PTC and PPMD for organizing the conference call and being so prompt to get this information to us parents!

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