What do Cadillac, Mack and Sally Brown, Seal and Scott Niedermayer Have in Common?

Yesterday, CureDuchenne was very excited to announce that Cadillac has chosen our organization to be their charity partner for the 2011 Super Bowl.  There has been a great deal of frustration among the DMD community that our voice was not being heard.  We all support and sympathize with anyone that has a severe medical condition; living with a child that has a terminal illness makes you very sensitive to other people’s suffering.  None of us want to detract from the attention that any disease receives; we just want our sons with Duchenne to have a voice also.  DMD patients and families got a large voice as of yesterday, thanks to Cadillac.

 It’s easy to follow the limelight and support a popular issue that the stars rally around.  What takes pure heart, compassion, courage and love, is to support a widely unknown rare disease like Duchenne.  I consider the GM executives, Mack and Sally Brown, Seal and Scott Niedermayer to be the early celebrity pioneers that put DMD on the map.  They will help us cure this disease by increasing public awareness which will increase funding for research and care.  You will be seeing announcements in the next few weeks of more DMD Champions that will carry our message to the public.

 I would like to publicly thank the GM executives who selected CureDuchenne and those that are working hard to implement this program.  Several times, we asked what we could do to help GM and Cadillac.  Every time they turned the conversation back to how they can support CureDuchenne.  This is a case of true philanthropy, it’s impossible to express my gratitude with words.  There are also others working anonymously behind the scenes that deserve a huge amount of credit…you know who you are…thank you.

The increased awareness for Duchenne that will come from our partnership with Cadillac will obviously help us raise the funds we need for research.   A less obvious, but extremely important outcome of this exposure will be increased influence on the regulatory agencies to prioritize DMD and also enhancing DMD as a desired target for biotech and pharmaceutical companies.  There are many moving parts involved in getting therapies to our sons, but this will only happen if people know what Duchenne is.  Ignorance is our enemy!

 In the world of DMD research, $1million funds a large research project.  $100 million would undoubtedly change the face of this disease.  I will offer this challenge to the DMD community…let’s raise $100 million and cure Duchenne.  And let’s do it in the next 3 years.  Can I guarantee this is the magic number?  Of course not, but I know it would dramatically improve our chances and the quality of life for our sons.  We will be presenting a roadmap within the next few months of how we can work together to achieve this goal.

 We need to think big and bold.  Following old models that have not resulted in a cure may not be the ones to stick with.   Cadillac and CureDuchenne will be announcing ways that the DMD community can rally together to raise a huge amount of money for research and many ways that we can let the world know…it’s time to Cure Duchenne.

The Who's Who of Exon Skipping for DMD and Beyond 

The FDA/NIH AON meeting in Washington DC on Monday and Tuesday included a fairly complete list of everyone involved in exon skipping from around the world. The attendee list included scientists, clinicians, biotech companies, NIH and FDA representatives and several non-profit organizations. Other diseases were discussed but of course, my main interest was Duchenne.

The conference was divided into four sections; 1) Preclinical Studies and Toxicology, 2) Biomarkers,
3) Clinical Trial Design/Endpoints and 4) Patient Registries and Assessing Long-Term Outcomes. Each section had a working group that had prepared for the last several months to present their findings at this meeting.

I must admit that the beginning of the meeting was feeling a bit like a regular scientific gathering where scientists present their research. But as the meeting progressed it became clear that this basic explanation of the science was necessary to prepare for the coming topics. There were clearly areas where AON drug development needs to progress before exon skipping trials are simple. Biomarkers and endpoints still need some work and coordination between registries could be improved.

Obviously, I had a bias in the kind of information I wanted, specifically, how soon will these drugs be available for our kids. A few specific questions for which I wanted answers were:
• Why are certain DMD drug trials allowed in Europe and not the US?
• How much human experience does the FDA need to see in foreign trials to allow them into the US?
• How many different exon AON’s need to be approved before the toxicology package can be abbreviated?
• How will we handle rare mutations that don’t have enough patients to conduct a full trial and justify a company’s investment?

And the answers…
When I asked when a foreign trial’s data/experience will satisfy the FDA to allow a trial in the US, I can’t say I received a satisfying answer. I understand there are very strict confidentiality issues between the FDA and biotech companies, but it seems that there could be clear guidelines for accepting foreign data.

Regarding abbreviating toxicology requirements for subsequent exons, the FDA did not feel there is enough data to agree that a similar backbone is enough to approve different sequences. The panel asked if after the second sequence we can move faster, this was considered a possibility, but surely not a definite. There was acknowledgment that for the rare mutations it won’t be possible to run phase 3 clinical trials.

There is no doubt in my mind that the FDA wants to do the right thing for patients. Are we expecting too much for them to share our sense of urgency? I don’t think so. Dr. Emil Kakkis from the Every Life Foundation has an initiative called “Cure the Process.” I was much honored to have Dr. Kakkis attend this meeting as a CureDuchenne invitee. He has offered valuable guidance regarding regulatory issues and is working actively to update the process of drug approval. I encourage everyone to support his efforts, please visit his site: http://www.kakkis.org/

Many people put a huge amount of time, resources and expertise to make this meeting happen.
Dr. John Porter from NIH, Dr. Anne Pariser from FDA, Dr. Francesco Muntoni from UCL, Dr. Kate Busby and Emma Heslop from TREAT-NMD, Dr. Eric Hoffman, Ed Connor and Abby Bronson from CNMC. The sponsors providing funding for this meeting were CureDuchenne, FED, MDA and PPMD.

In summary, I would say this laid a very good foundation for future interactions regarding AON’s. This meeting clearly showed the DMD community where we need to improve and close the gap to come closer to FDA standards. I think the DMD community still has a job to do to express the urgency that we have, but I believe we can communicate in a more unified and productive way now. After several one-on-one conversations with the regulators, I personally feel there is a more open communication path.
I’m hoping that this will result in a balance between the risks of new drugs with the knowledge of what happens to our sons if we do nothing.

I will be coordinating with the various groups to see how we can keep up the momentum and hurry this process as much as possible. I’ll report back with any updates.

Debra Miller
President and Founder

On the eve of departure for the NIH/FDA meeting in Washington DC, exon skipping is on the minds of many people who are touched by Duchenne. Not that a treatment is ever far away from our thoughts, but right now, there is great focus on making sure that things are done right to avoid unnecessary delays.

Earlier this week I had the pleasure of attending the AON Biochemical Outcome Measures workshop in London. CureDuchenne sponsored this workshop, along with FED, Ryan’s Quest, Charley’s Fund and Duchenne Ireland. Exon skipping experts from around the world gathered to share data and collaborate on the best way to evaluate and quantify dystrophin.

Sitting at dinner with Drs. Steve Wilton, Kevin Flanigan, Eric Hoffman and Francesco Muntoni, I was able to see their passion for finding a cure for DMD and to witness their great ability to identify the roadblocks and address them. It was wonderful to see researchers from the corners of the globe come together and openly share their work.

On Monday, you will be able to attend the NIH/FDA meeting via webcast:
http://www.cvent.com/EVENTS/Info/Custom.aspx?cid=35&i=755d1ae3-2f20-4849-8ba4-91a9e0a9e847

I am among many parents who are dismayed to see the United States being excluded from DMD trials. Last year at a TREAT-NMD meeting, I was surprised to hear a parent organization being so openly opposed to US patients participating in European trials, even though patients are allowed to cross borders in Europe to enter trials. It would be nice to see the same level of cooperation on this matter as the researchers from around the globe are showing.

No one expects to see the FDA change their requirements on the spot next week. The stakes are high and this is the time for us all to rally together to effect change. We need to see DMD trials in the US now. I’m really hoping that the DMD community will logon in mass to the webcast on Monday and Tuesday. My belief is that all patients and parents need to educate themselves and be part of the solution.

CureDuchenne was the first DMD organization to fund a biotech company dedicated to exon skipping. Our funding of Prosensa came at a very critical time in their development and their recent partnership with Glaxo Smith Kline will contribute up to $650 million to Prosensa’s DMD program. CureDuchenne also collaborated with FED and the DoD last year to enable AVI to get FDA clearance to move forward with their trials. We applaud the contributions of foundations to identify technology early and enable it to achieve proof of principle, but in reality, the dollars that all the DMD organizations put together are a very small percentage of the drug development costs for AONs. The more that academic, non-profits and industry can work together, the better.

I look forward to reporting back to you next week (don’t hold me to that, my blogging is a bit intermittent).

Debra Miller
President and Founder
CureDuchenne