The AON meeting in Washington, DC will be streamed. And we all sit on the edge of our seats, anxious to see exon skipping in trial, analyzed, and approved. We have heard bits and pieces of the first exon trial skipping exon 51. Press releases and rumors about the presence of dystrophin and what that means are rampant, and we still wait and wait for something, some news, some information, something about the IF and WHEN this might apply to your son. I thought it might be useful to provide some detail about what happened, how this meeting was developed, and what is hoped will be the outcome.

Last year, a meeting was held with EMEA (now EMA). This is the regulatory agency for Europe and while each country has their own specific regulatory requirements and issues, the EMA makes overall regulatory decisions. There is a lot of discussion about exon skipping and the promise of this technology to ‘snip’ together our sons ‘genetic recipe’ so that it restores the FRAME or restores the cell’s ability to make sense of the genetic information (recipe) and produce dystrophin, not the original recipe, but a shortened form. Something useful. Something that would place this shortened version of dystrophin right under the cell membrane and restore its connections with all of the other associated proteins. Something that would restore integrity to the muscle cell to some extent and slow the cascade of degeneration within muscle. And early results indicate that, at least in some cases, skipping one or more exons and restoring the frame does restore integrity/stability in the muscle cell and does, in fact, slow degeneration. At least that is what we know from cell culture and from animal data.

The community (research, clinical, family, people with Duchenne) want regulatory agencies to understand that this strategy is critical for many, that this strategy is likely to preserve function longer and buy time. This strategy is HOPE. And we all wanted to impress regulatory agencies to consider ways to streamline the process. For instance, if exon 51 clinical studies prove it to have benefit (efficacy), then would they consider, for instance, approving the backbone chemistry and modifying requirements for other exons, such as modifying the toxicology package, the clinical studies, and approvals.

During this meeting researchers presented data (animal data, safety, toxicology), clinicians discussed clinical studies, ethicists discussed risk/benefit and the ethics of children in clinical studies, informed consent, and to my mind, most importantly Elizabeth Vroom presented the patient’s side, starting with a video of 4 young men with Duchenne, discussing what THEY wanted/needed, what they believed would improve their quality of life. Elizabeth’s son, Justus, talked about the accommodation required to move his hands from his lap to a table, using his fingers to ‘walk’ forward, to ‘walk’ to meet his elbow, the lever approach to lift his elbow and ultimately get his finger into his mouth, and then his head to pull that arm onto the table. This demonstration, the ‘finger walking’, the ‘lever’, the accommodation, very familiar to all of us in the world of Duchenne, but very unfamiliar to regulatory agencies, provided with a ‘library’ of documents to sift through, was heartstopping and illustrative.

The meeting in Washington is a follow-on, on this side of the ocean, to talk about the same issues. The community (research, clinical, young men, and their families) believe in this approach and are interested in pursuing methods of streamlining the process, perhaps novel new approaches for clinical studies (N=1 or a few) to accelerate exon skipping as a potential treatment, to accelerate, not just the exons in the 40-53 area that are presented at meetings, but ‘skipping’ early for rare mutations and duplications.

We cannot expect Ann Pariser (FDA) or Rusty Katz (FDA) to end the meeting with decisions. Keep in mind that FDA has to react to a sponsor’s submission and does not speak in generalities. But at the end of the day, when Dr. Pariser /Katz and others go home, we want them to dream about Justus’s accommodation, think about all boys who might benefit from this strategy, and understand TIME. Buying time is the critical factor. The stakes are high, the risk is great, and TIME is critical.

The NINDS/FDA Antisense Oligonucleotide (AON) Therapies in Neuromuscular Disease Conference will stream live on September 27 and 28. Click here for more information, including webcast details and a full agenda.

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Comment by Pat Furlong on September 26, 2010 at 10:19pm
Cheryl, I will be taking notes and posting my notes. There are no confidentiality issues, this is a public meeting.
The FDA will not give a time frame. Our goal is to inform FDA, to discuss in detail issues around AON and to convince them, that once the first 1-2 exons demonstrate efficacy, they will consider streamlining the approval process in order to expedite treatments for all persons with DMD likely to benefit from this technology. Keep in mind, FDA will not give specifics or time frame - we will come away from this meeting with a more well-informed FDA. They will see a community very interested and willing to partner with them in any way possible to move this forward as quickly as possible. This is all about being proactive, being in front of FDA, speaking in one voice and providing the assurance that the patients carry the highest risk, bear the greatest burden and have no time to waste.
Comment by cheryl cliff on September 26, 2010 at 2:56pm
Beautiful, Thanks Keith!!!
Comment by Keith Van Houten on September 25, 2010 at 9:14pm
FYI, I sent a note to the webmaster of the webcast site asking if it'll be archives so we can watch it after the event. I'll post if I hear something.
Comment by cheryl cliff on September 25, 2010 at 1:03pm
Very glad you are doing this Pat. This meeting is monumental to me.

For those of us who cannot listen to both days of webcasts will PPMD provide information afterward? I imagine providing the webcasts in a text format would be lengthy but I assume there should be no confidentiallity issues with doing this. After all, this is defined as a public meeting, right?

And while we can't expect FDA to end the meeting with decisions, are we at least offered some kind of timeframe as to when they will come to a conclusion regarding our issues?

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