After all this time and all the data, it amazes me some of the ignorant issues/commentary that still linger regarding Etep. First off, while the CG can compliment the FDA for their willingness to do a "collaborative" review of the dystrophin data, what the hell have they been doing for the past year? Unless I missed something, the FDA has not clarified at all what they consider to be a valid dystrophin measurement, but at the same time is still pushing for a 4th biopsy - what has changed since November? The other comment about the FDA not being "comfortable" with 6MWT data because of the open-label nature of the extension study is just mind-blowing - as if you can "coach" a boy into overcoming the loss of muscle function. I did not get the sense the FDA's knowledge of DMD or the validity of the clinical results had evolved at all since November - perhaps their completely ignorant position that the stability experienced by the Etep boys could be explained by "variability" in the natural history of the disease has tempered somewhat.
When it comes to the analysts, not much has changed, either - how many times did you hear the word "correlation" used in yesterday's call - some of them are still hung up on the idea that you can't prove efficacy until you can somehow correlate the dystrophin data with the 6MWT data - as if there SHOULD be a formula indicating a XX% dystrophin positive fiber measurement translates into a YY% change in 6MWT.
Somewhere along the way the fact that these boys are experiencing an unprecedented and borderline miraculous stability/improvement in their muscle function has been lost in the sea of extraneous issues of how this benefit should be measured. It is sad how the same analyst who would celebrate a 3-month change in median survival for a group of cancer patients as some sort of blockbuster event would look at the Etep data (12 of 12 boys showing dystrophin production & 10 of 10 ambulatory showing stability) and think I'm not sure?
You are likely correct. Simp would have everyone believe that CG canceled the JMP presentation due to "complicated" data points coming out of the 144 week data. We know from parent reports that at least 3 boys were likely to show improvement in their 6MWT performance, but there is still a great deal of uncertainty about what the ultimate long-term clinical outcome will be for these 10 boys - will they all remain ambulatory; will some slowly improve their mobility as they age, while others slowly decline (depending on the state of damage their leg muscles were in at the start of the trial); how will the drug effect their heart muscle; will higher doses make a difference; etc., etc. I don't view these issues as a knock against Etep or whether it should receive AA, because it will take decades to answer a lot of these issues, and that is the reason the AA regs were written - i.e. to give patients of rare, deadly diseases access to promising drugs before the full clinical benefit is understood. So, if a few of the 10 boys start to show signs of decline at w144, while a few show signs of improvement, does that taint the "promise" of Etep and would it be reason enough to withhold AA? I can't imagine that a panel of experts, let alone Hoffman, would conclude that. To expect every boy in this targeted patient group ( 7 years of age w baseline 6MWT under 350) to respond the same to Etep is a ridiculous premise. The fact that up to week 120 they have all showed signs of "stability" is astounding - any aberration off of that track would not be "complicated", it should be expected.
jrrt1 - your comment on "redeemable muscle" is key. I think this is where some of the ignorance on the short side lies - Etep does not allow previously damaged/destroyed muscle to be restored - it only prevents further damage to the existing functional muscle tissue. If the Becker's theory holds, it is still unclear what the long-term prognosis is for some of these boys that have already started to decline. It is obvious that a boy that has already lost ambulation will not regain ambulation and the hope is that boys treated early in life will never lose ambulation, but these boys that begin treatment when on the cusp of beginning to lose ambulation (7-9 years old) are in a gray zone - will their existing functional muscle grow with them as they age and allow them gain strength and avoid the wheelchair? I don't think that question will be answered for decades and it won't be absolute for every boy. Some of the recent anecdotes from the parents about their boys gaining strength or "improving" in functional tests offer some hope that they can gain further muscle function as they age, but only time will tell. Either way, Etep is the best hope they have for dealing with DMD.
Anybody that is still discussing SS doesn't get it. Statistical significance in this trial was defined as the difference in the change of 6MWT distance between the treated group and the placebo delayed group at 48 weeks - that difference of 61 meters was statistically significant. The fact that this differential has held up over 120 weeks (it was 58 meters) is not important - what is important is that both groups continue to be stable. Would the results at 144 weeks be more meaningful to you if the placebo delayed group dropped by 30 meters, while the treated group remained stable (thereby increasing the differential and statistical significance)? Of course not - what is important is their 6MWT scores continue to NOT DECLINE. The other side of this hypothetical coin is what if the placebo delayed group increased their 6MWT at 144 weeks by 30M, while the treated group remained stable, thereby cutting the differential in half and losing SS - would you consider that a bad thing? SS between the treated and placebo delayed groups is meaningless at this stage of the trial - they should be considered one group of treated boys and as long as they continue to be stable or improve, that is what is significant.
Correct - No stupid questions, but a lot of gibberish on your part. The reason the reported "progress" of boys like Billy, Max and Sawyer are "exulted" is because their improvement over a period of 2 years is unprecedented for DMD boys their age and the "failing" to mention the progress of the rest of the boys is because their parents aren't providing public updates on Twitter or Facebook. The FACT that all of the boys may not show improvement or stabilization going forward has been discussed at length on this MB - it is clearly understood that there will be no "single outcome" for boys aged 7+ who begin Etep therapy after already having material damage to their muscles. The FDA has not had a "rigid adherence to science based evidence" in dealing with Etep - to date they have shown a complete lack of understanding of the science of DMD and have dismissed the current data to date based on their misunderstanding of the natural history. The idea that the FDA is going showcase its "power to choose winners and losers" by stacking the advisory committee with experts that may have an agenda against SRPT is ridiculous. DVAX has a vaccine that is competing against an existing, approved product that has been used for years - pushing safety issues when there is an effective product on the market is a little different than playing political games in the face of dying boys. You need to get a grip on reality.
What a loser post - "SRPT should stop the shenanigans and get busy with the P3 trial design" - what do you think they have been pushing the FDA to make a decision on since Nov? The only thing dumber than your post would be for the company to start the P3 without getting sign-off from the FDA on endpoints, control group, etc. The idea that the delay in the clinical process has anything to do with SRPT is absurd - they have provided the FDA everything they have asked for and more on a timely basis - it is the FDA that is dragging the process out.
Sawyer's mom, who reported last month that her son more than doubled his running endurance in a "Pacer" test at school, reported on Thursday that Sawyer's 6-Month check-up showed "Improved Strength, Improved Lung Function/Capacity and increased ROM (range of motion)". At some point, even the most clueless naysayers will have to acknowledge that the improvements these boys are experiencing on Etep trumps any issues about dystrophin measurement issues, Intent to Treat issues, and any other neurotic issues they may have about the Phase II trial. Reasonably likely? Not even close - it is "bloody obvious" that this drug works.
At some point these stories will hopefully become boring - ho hum, another boy's life (and quality of life) saved by Etep - but for now, we need to keep hearing them until all the doubts and meaningless issues delaying the approval of Etep are swept away. IMO, the fact that it will be another year+ before boys outside the clinic get access to Etep is criminal - the "objective" evidence of boys stabilizing and improving over two years is overwhelming. The scary thing is that I think the FDA is so ignorant and fickle in assessing this drug, that if one of the boys in the trial suddenly had a significant decline in their 6MWT, they'd toss all the results out as being meaningless. The fact that Etep has to perform flawlessly in order to be validated is ridiculous, so just count your blessings that Etep is as good as it is.
If SRPT's issue is a lack of "n", RNA's issue is too much "n" - i.e. too many patients with injection reactions and kidney problems and more than enough "n" to produce a statistically significant efficacy result if it was there. That is what seems to be lost on most bashers - you could dismiss an n of 12 if only half of the boys were stabilized, but when 10 out of 10 ambulatory boys are stable after 2 years and 12 of 12 show stable/improving pulmonary function, it is clueless to talk about statistical significance.
Because he is an idiot. As one of the clinicla experts at the FDA panel back in Feb said - "it is bloody obvious" that Eteplirsen works. The people that have bashed the drug or the trial results don't understand the disease and are caught up in the usual FDA statistically-focused straightjacket that doesn't allow them to see the obvious. The FDA is being forced to educate themselves on the disease and think outside the statistical box by the parent/patient groups. What is obvious to the experts today will be even more obvious a year from now when the FDA has to make a decision and the boys in the current trial are 13+years old and still ambulatory.
As I stated in my last reply to your gibberish, you start with false premises and a clear misunderstanding of the existing facts - once again, you did not disappoint. You use this term "complicated" based on delusional interpretations of the existing data. Anybody that has a clear understanding of this disease and the status of the boys enrolled into this trial knows there is nothing "simple" about the trial or the resulting data. For every boy that increased his 6MWT distance from w96 to w120, there was a boy that declined. If you are delusional enough to believe that if Etep works, everyone should be increasing, then you might view this as "complicated". If, however, if you accept the fact that there are no absolutes for this disease or trial, you accept that there will be some variability from test to test, but also have a clear understanding that if Etep was not working that at least 1 or 2 or 5 of the boys would have shown a meaningful decline in 6MWT distance by week 120 - the fact that none of them has is not "complicated" - it is simply astounding. Just as I stated in my last retort, the rest of your points are delusional fantasies of what is going on behind the scenes - the most delusional being the "CEO advance discloses to the FDA" data from this trial. I know it is politically incorrect to say so, but you are #$%$.
The reality is that the FDA always had the "cover" of waiting until mid-late 2014 in order to make a decision, because SRPT needed that time to get the manufacturing in place and get the Phase III started. The time they have wasted by telling the company not to file for AA is that if they change their mind, SRPT is now 3+ months behind in getting the filing prepared.
Pack it up pasteur - your garbage posts are getting tattered and tiresome. The number of patients in the trial had nothing to do with limited resources or manufacturing capacity. There is a reason all your posts get unanimous thumbs down - you are not a contrarian - you are a douchebag!
I love it when people lay out their stupidity point-by-point - all five your points are so far off base from reality they don't even warrant a reply. Why do you feel the urge to expose how clueless you are in this fashion?
A number of posters have tossed out the idea that the Etep results should be viewed in a context similar to a cancer trial - i.e. benefit is typically proven with well less than 100% of the patients having a response to the drug. While there is some merit in this thinking, it also distorts the picture by missing a key factor that Etep's clinical path has in its favor. The merit is obviously in the fact that we know that Etep is not a "cure" in the sense that a patient already having material muscle damage from DMD will not be able to recover that damage, so the "response" to Etep as measured by clinical benefit to motor function will not be 100% in a patient population of boys aged 7+ years - they already have substantial muscle damage that may not allow them to improve or even stabilize. Ultimately, the clinical benefit that is most important is survival, but trying to measure the impact of Etep on survival would take too long and be grossly unethical (assuming you had a placebo arm). This set of circumstances is exactly why the accelerated approval rules were written - the ability to measure clinical benefit is difficult in the short-term (not only due to the slow, progressive nature of the disease, but also the lack of a large patient population) and is why you can't compare Etep's results in the same context as a cancer drug. Most cancers are progressive enough to kill their victims within a couple of years and most cancers have a current standard of care that provides some benefit, so the ability to measure clinical benefit is typically very concrete. Etep should not and will not be held to that same standard in an accelerated approval setting.
What rock did you crawl out from under and why did you decide to defecate here. Obviously, you are clueless as to this company and its prospects, so the only mystery is why you felt the need to prove it to this particular MB?
Here we go again - the company puts out a timeline for filing and potential approval and people feel the need to fantasize on how that could be accelerated. There were several specific reasons why the filing was targeted toward year-end, including the very important requirement that the confirmatory trials be started and enrolling prior to the filing, but all those reasons get pushed to the side in order to masturbate over the idea that the filing could take place months sooner. I don't get it - do you really think that a filing in Sep would impact the value of the company dramatically vs a filing in Dec, or is this just the case of people sitting on options that expire before Q4 clinging to some hope for a bump before then?
Just reiterating the same goals they have had since last November - get the sign-off on a Phase III/confirmatory trial design and get that started as soon as possible and then work on reversing the FDA's decision on AA. Whether AA is in the cards, they need the Phase III trial to get moving.
He wants to be a "headline" presenter at a conference in Oct, which usually means they have to limit the information publicly disclosed beforehand. The headline data will be available over the next 30 days - my sense is that the data will be too good to hold back - we've already heard from a few of the parents speaking to "improvements" that their sons are showing in their latest tests.