On Monday, I attended the meeting in Washington, DC focused on AON. It was Elizabeth McNeil (OOPD) who suggested this meeting in Brussels last year, following the meeting with EMA (formerly EMEA - the European regulatory agency). Elizabeth suggested it would be important to open this dialogue with FDA and suggested that she would discuss this with Dr. Cote (OOPD) and leadership within FDA. The committee was organized and after numerous calls, discussions, the final agenda agreed upon. Unfortunately OOPD elected not to support the meeting and thankfully Janet Woodcock (FDA) and Anne Pariser (FDA) stepped in. With the leadership of John Porter (NIH), Ann Pariser, Emma Heslop (Treat NMD), and Abby Bronson (CNMC) and a number of organizations providing additional financial support (PPMD, MDA, FED, and CureDuchenne) the meeting was scheduled. I am hopeful many of you were able to watch as the meeting was streamlined, but for those who were unable, John Porter has provided the following information:
Increasing the level of interactions among the stakeholders in an emerging area is always a good thing, and I think we accomplished that. Moreover, I think there are some clear opportunities for moving forward on the regulatory science discussions, particularly in two areas—biochemical/muscle strength biomarkers and data sharing on AON backbone tox.
• NIH will work with FDA and some of the participants to put together a brief meeting summary that I will try to get out to you very soon for your distribution or web posting.
• I will be seeking permission to post the presenters/working group PowerPoint presentations on an NIH website and will give you that link when available.
• And then there will be a more complete conference summary that at least will be posted on the NIH website with links for you—that may be written up for publication also—need to see what we have when the information is aggregated.
• I’ll try to make all of this happen as rapidly as possible; please remember though that I have to seek clearance on such releases.
• We did not archive the webcast.
I left the DC meeting to participate in discussions with industry and regulatory agencies in St. Louis and later the HRA meeting in Chicago. I discussed biomarkers with several individuals from FDA/CDER. And it was interesting to discuss biomarkers in general and the difficulty confirming biomarkers in any disease indication.
The major biomarkers are for common conditions, as in cholesterol. Low cholesterol means less stokes, less heart attacks. And it took years to get there. In our world, the community has read, listened to, and watched mouse studies where dystrophin is seen as a ‘halo’ around the cell and we all know, the more dystrophin, the better. But it is not quite that simple. We know that if a person is born with dystrophin, they do well. We also know that individuals born with truncated (shortened) versions and depending on the quality of that version, they may do well. (We have heard the story of the 65 year old playing tennis with Becker).
But what we do not know at this moment is what happens when you replace dystrophin in a person born without dystrophin. And to a large extent it will depend on WHEN you are able to replace dystrophin, the quality of the dystrophin protein (not all in-frame proteins are alike) and the cellular environment (how much fibrosis, how much fat) and at the end of the day, the biomarker has to be able to suggest that X% of dystrophin relates to X% improvement or X% slower degeneration or X% change in ability. There was considerable discussion about biomarkers: the difficulty, the lack of current knowledge, the urgent need. Several of the investigators said strength. It is all about strength. I think we would all agree.
Sharon and I are preparing a full report. We will do our very best to post by mid-week next week.