Comments by festivus from this past weekends meeting ; part 1
Here is a writeup of some of what was discussed at the PPMDconnect conference. I tried to be as accurate as possible, but if anybody else watched the webcast, let me know if I missed anything, or need to correct anything.
Disclosure: I am long SRPT
There is a summary at the end with my comments.
Overall, the respective companies have already previously discussed most of the things mentioned.
Dr. Bob Temple
- Orphan diseases can have pivotal, small, single arm trials
- If there is a clear signal of clinical effect then it’s not really the size of the trial that matters
- Often historical controls are used, but the current exon skipping drug trials all do have placebo controls, at least initially.
- Specifically, surrogate marker of Becker-like dystrophin biopsy is a question, answer has been decided, but cannot reveal, and was trying to sound as impartial as possible.
- States that it is produced in the muscle so whether it gets to correct location is not an issue.
- Suggests that more of it is probably better than less, and it’s still a question of whether this type of dystrophin is clinically relevant → this is the question for whether it’s a good surrogate.
- States that it is good to be able to correlate surrogate with a clinical endpoint to prove validity.
- Stabilization over a year and a half, or stabilization after an initial decline can potentially be persuasive, if this is not expected based on natural history → seems like both are reference to Sarepta trial → I will discuss natural history at the end.
- Didn’t catch the beginning of the talk
- Want to incorporate immunofluorescence (IF) intensity into dystrophin IF measurements (as opposed to just % positive dystrophin fibers)
- Dystrophin IF from Becker patients didn’t directly correlate directly with disease progression.
- Looking at other measures, such as miRNA profile of dystrophic tissue & MRI for surrogate markers.