Can anybody explain for me why the CK reduction was UNEXPECTED?!!!!!!!!
Moreover,why not all patients had this reduction?
I have just had a quick second listen through and am unable to find the use of the word "unexpected". My impression was that it was an "intriguing" result.
I am also not convinced that only some of the boys had reduction. I believe that it was the majority boys.
I would like to add though that to clarify it would be best to contact the company.
Not sure why they said CK reduction was unexpected. My guess is probably because the drug was given only for 10 days and was not expected to upregulate Utrophin enough to stop or slow down muscle degeneration. Please keep in mind this was only a safety/tolerability and dose finding study. NOT a efficacy study.
I think the answer to the second one is because of their observation that the absorption of the drug into the blood stream varied widely between subjects in the trial and was not similar to the earlier P1a study in healthy adults. Again, my guess would be that in those cases where the absorption was low, the upregulation of Utrophin probably was low too and correspondingly the CK levels would not have come down because of that.
I think that's about right. CK reduction unexpected because it was only a 10 day safety and dosing trial, rather than they don't expect it to work. My understanding was also that it was in the majority of boys, not just those that had better absorption that CK levels reduced. I suspect they still need to dig deeper into the results to understand the variations. Interesting the effect of the ultra low fat diet on absorption. Understandable given it's an oral dose.
They are now looking to see if they can add fats/sugars to the dose itself so that it carries it's own assistance to metabolise rather than having to ask boys to change diet. Another interesting side point is that they have lots of the drug already manufactured. It has a long shelf life and is both reasonably easy and relatively inexpensive to make. They still hope to go straight from phase 2 (in EU/US) to approval, IF things continue to work out.
I'm not a parent of a DMD boy, but do many parents have their kids on low/no fat diets?
Are all these boys on Steroids?
I consider the real encouraging result when no exeption for its success,do you agree?
I am afraid that this drug needs to be formulated again and takes longer time to go!
Was the drop in CK sharp?
I was informed that many trials which failed also showed a reduction in CK!so it is not alwayes indicates that the drug is functional.!
David, mainly because of the 6MWT, I suspect all trialists will need to be ambulatory to be included. If it works (to be proven yet) might be able to get it on compassionate grounds? Hope so for you're and the other parents with kids who are more advanced.
As to the fat content, of the 5 parents that kept a detailed diet sheet, the 4 who had low/no fat diets had a lower absorption, so would appear to be a correlation (but again I think this is something they will need to go back and check to be sure that's the reason rather than some change in the GI tract caused by DMD).
"Another interesting side point is that they have lots of the drug already manufactured. It has a long shelf life and is both reasonably easy and relatively inexpensive to make. They still hope to go straight from phase 2 (in EU/US) to approval, IF things continue to work out."
This all sounds fantastic. Obviously have to move forward with a degree of realism, but.. it's safe, it's not expensive & it could work on all dmd boys??
Would anyone with more insight than myself care to guess what sort of time scale would we be talking until it's available, if this is approved?
Phil, 2016 would be my best guess, if they get good results and the FDA allow accelerated approval (which looks more likely post the efforts by PPMD). Lot's of if's but recruitment would be fairly straight forward as they can choose from the full DMD pool (rather than based on a particular exon) and it's oral rather than by injection, so much easier - and less painful - to admin. However, biopsy's still needed to demonstrate it's efficacy. Quite right to be skeptical at this point but just might be a small light somewhere on the horizon.
NO PHASE 3 IS NEEDED FOR APPROVAL?!!!!