At 4 years, the difference in mean 6MWT-change is 162m (with n=11 for EC, and n=12 for Etep). Not sure how you are getting 60m only (must be inaccurate, since Sarepta also gets 150m at 3 years).
Q1. Its not clear the graph represents 4.5 years of data. E.g., you see some colored lines correctly ending at 4-years --- 13.9, 13.9, 14, 14.2, 14.3 years. But, some do extend -- so likely Farkas has screwed up again in plotting the graph (there are many other inaccuracies in the BDs.
Q2. I don't think so. But, Dan S of Boston Journal was able to dig up something. But, it shouldn't matter. Figure 18 of SRPT's BDs says it all.
Yes, this damage will take a lot to reverse. If they raise cash within a year -- the dilution would be much worse either way.
I should add that FDA had the 4-year data from SRPT, but NOT from the EC (which is of some significance). Plus, if you read the footnotes, it also states that the remaining three EC boys lost ambulation at 4.5 years and 4.8 years.
Major means "significant" and/or "substantial" -- that requires more consideration. Or it could just be an excuse to take more time (due to snow or otherwise).
Yes, if FDA had already made up their mind to reject, they wouldn't need this delay.
If you read FDA-BDs carefully (see Figure 9 to 13), FDA BD was already based on 4-year data.
Most importantly, all of FDA's criticisms (chiefly among them: disparity between the 201 and EC subjects, low WB numbers, NSAA decline rates, etc) remain intact.
BUT, science aside, FDA may be trying to save its face here -- by USING THIS EXCUSE to change things. That's how I look at it.
I'll be very shocked if BDs tone/content changes substantially --- there may be an addendum to correct the predictions of LOA age of Etep boys --- that's about it.
TO ME, none of this matters. I am a strong believer in Etep's approval -- unless something negative comes out of trial results -- irrespective of these inconsequential events.
The original post is out of that paragraph -- that Etep boys decline 3.6/year vs EC at 4.6/year. SRPT is claiming that that difference does result in true clinical benefit over 3 years -- and no arguments there, but I just expected/desired/hoped for more.
Also, literature suggests that an NSAA score of 9 and 13 imply 1 and 2 years from LOA respectively (in untreated boys).
Yes, that's one interesting way of looking at my objection to predicting LOA age from NSAA scores in Etep boys. Thanks.
There are two scales on NSAA scores (linear and raw). For the raw analysis (34-score scale) used by SRPT, the average decline is 4/year for boys greater than 7 years (Ricotti 2015). This is based on a 8-year long study -- so, should be considered credible. Your numbers of 8 points and 14 points are for the linearised NSAA where the scores are out of 100.
More importantly, the EC group used by SRPT had a decline rate of 4.6/year over 3 years -- this can't be argued with.
Yes, please, don't waste time with me (put me on ignore) --- I certainly would put you on ignore (I don't have time for useless people).
The problem is dilution. SRPT burns $200M/year. If the P3 results come out in 2018 --- then the approval will happen in 2019. So, we are talking about $600M of expenses from now till then -- which essentially mean about 50% or more dilution. Thus, I would guess a pps of $30-50 post-approval and post-dilution, which means .... the current price would be $5-$10 given all the uncertainly and the time to approval.
I think if the AA doesn't happen -- SRPT will look for a partner and/or sale, or it will have to cut its expenses drastically (in half or more).
***By FDA's own "admission" 6 of the boys should be non am according to nsaa scores***
How so? At 3 years, I see only 4 boys with 9- scores. So, yes according to FDA, 4 should be non-ambulatory -- and 2 actually are.
Field: I'll be shocked to the core -- if it was legal for FDA staff to own stocks that they are reviewing. Can someone enlighten me on this? If not, I'll try to find out the fact.
That would be extremely illegal -- I doubt Farkas (or any FDA staff) would risk jail-time and/or their career for the sake of some money. Recall -- Martha Steward, etc. Maybe, 15-20 years ago, people may have risked it -- not any more, imo.
As I mentioned in another post, I believe the weakest link in SRPT's data package are the NSAA scores. Some observations:
On an average, NSAA scores of Etep boys had a decline rate of 3.6/year vs 4.6/year for the EC. Some of the studies in the literature suggest a decline rate of only 4/year for boys 7 years.
If you remove the 2 non-ambulatory boys, then the decline rate of Etep boys improves to 3/year (decreases from a mean of 26.1 to 15.3 over 3 years).
Most surprisingly, NONE of the boys had any non-trivial INCREASE in yearly NSAA score. This seems to contradict the patient testimonies of the kind that the subject was able to perform certain tasks that he wasn't able to perform before.
I believe that the NSAA scores trend is not terrible -- its good enough to SUPPORT the main pathway of 6MWT as the intermediate clinical endpoint, but the trend certainly disappoints me (rather my earlier higher expectations).
Harry: Likely, and that's exactly my thesis too (that's why I recommended you to "buy it all"). However, I want to confirm that thesis by looking at the most positive BD out there -- I'll try to search and see what I can find.
I do NOT believe that FDA (or any of its staff) is in the business of manipulating stock market. You may call me naive -- but I am willing to bet on it (however, it would be impossible to prove one way or the other).
Yes. Just to make one correction: Technically (I posted the FDASIA law link), the FDASIA doesn't advocate lowering the standard for efficacy evidence (unfortunately, you and I, may say).
I understand the purpose of BDs, However, I want to carefully read the most positive BD out there (hence, asked for pointers) -- and based on that try to make a judgement on the real intention of FDA behind SRPT's BD.
**J-H-C, you're thick.**
Just so you know -- you are more dumb than you may think. I don't have the inclination to debate/argue with a dumb arrogant ^&*( like you. All you know is IHA vs WB --- and you never lose an opportunity to boast of that knowledge! Trust me, you don't know much else. As I said -- I have no inclination to prove how dumb you are (you expose it quite easily yourself). Over and out.