The other thread I was just looking at got a bit messy, so I thought I'd cut through the clutter. The twitter post about age and 6 mwt is absolutely correct. If you go to the study, click on the link for Table 1. Ignore the top row (whole cohort), because it blends all ages. Look at the next row. It gives the results for below age 7. The third column lists changes in 6mwt. For these young kids, the mean (or average of all results) was an increase of 27 meters. Now go to the next row, which gives results for above age 7. This is the age group more directly applicable to Eteplirsen's trial. In that age group, the mean was a DEcrease of 37 meters (not 27 or 22 as erroneously transcribed in the longer thread).
Now if you read further you can see the 21 meter DEcline in exon 51 patients, but remember that number INCLUDES patients under 7. So it understates the amount of decline that would be expected in an exon 51 cohort comprised only of kids over 7 (like the eterplirsen trial).
This new study is in line with other recent ones looking at over age 7. Mazzone (2013) had it at -43. Goemans at -42. Ataluren IIb placebo -58. McDonald (2010) at -115. and Drisapersen pIII placebo -83.
Only eterplisen is an outlier.Finally, for the sake of comparison, remember that if you honestly want to know if the drug works, you should compare the results of the eterplirsen trial not to change from baseline but to change from the time when dystrophin production kicks in. For the first 24 weeks or so, eteplirsen kids will decline just like anyone else. Only after that will you see the sharper distinction between treated kids and natural kids.
So, for example, the fact that the original treated kids have only declined 13.9 meters in 2 1/3 years versus natural history of 37 in just one year understates the efficacy of eterplirsen.
I start wondering if there will be a Phase III at all. Its a waste of time. Either FDA changes its mind and accepts AA, or might as well continue treating the 12 boys in 2014 and meet again with the FDA later on with additional evidence on their health.
Even if AA a kind of study, or 'Ph III' would still occur. IMO, even in the case of AA, there should be data collections on all who receive the medication to follow clinical status---6MWTs, upper arm strength and pulmonary function testing. These should be able to be done by the individual providers caring for the boys. Alternately, even with AA, a set number of boys could enrolled and studied as SRPT doing currently (+/- with muscle bxs) and a matched control from another deletion set of patients be recruited and tested clinically in parallel (no bxs--just functional tests alone).
Unacceptable to me, and possibly undo-able, would be with a placebo controlled, blinded study. This would be a terrible outcome and may never get done due to parent's rebelling; or, IRBs at institutions reviewing existing data and considering it unethical to have such a placebo group in their institution; or, the 'n' required would likely make adequate enrollment very difficult. This would be DMD communities nightmare and a dream for cynical shorts, IMO.
What I hope will happen is approval with other-exon-control matched group; AND, as a clinician, collection of above data for all boys treated.
Yes, there will be a new study regardless of AA, and no, it wouldn't be a waste of time. I think AA should be given, but the P2 study was small. We need, and the FDA will demand, to see results from a larger study, as they should.
a new study is mandatory and the company planned for it all along, whether designated as a p3 pivotal trial or a confirmatory study ......the FDA has always said they will need to see more pts treated to enlarge the safety database before approval, so its not a waste of time
Any way you cut it, the FDA's position that the "variability" in the natural history data could explain the stabilization seen in the Etep patient group is flat out wrong - lets hope they have the professional integrity to acknowledge that and we'll be one step closer to AA.
fxxx... Thanks for this. I was the one who erroneously pointed to the declines of (27 and 22) but in my defense, I was struggling to understand what they were trying to say as this was the first time I had looked at this type of data. Please understand that is wasn't intentional, just a hardware guy who dabbles in Biotech investing.
Really appreciate your clarifications.
Sentiment: Strong Buy
A coherent writer at last! On your final point...I'd been wondering about that recently myself. Have you calculated what the gain in meters walked by our kids has been from their low at 24 weeks up until their 120 week results?
You: "Finally, for the sake of comparison, remember that if you honestly want to know if the drug works, you should compare the results of the eterplirsen trial not to change from baseline but to change from the time when dystrophin production kicks in. For the first 24 weeks or so, eteplirsen kids will decline just like anyone else. Only after that will you see the sharper distinction between treated kids and natural kids."
If they averaged a loss of more than thatt 13 meters (their current decline from baseline) from day one to week 24 (where dystrophin has kicked in finally), then they should now be showing an improvement from how they were doing at their worst point (week 24).
It's funny that Chris has never pointed that out. Maybe he's waiting a bit longer as it seems that at this point many of our kids are now bettering their distances.....?