grey - While under most circumstances, continued stable results in an extension trial would not be considered material, I am having a hard time agreeing with that position when it comes to Etep. Given the slow, progressive nature of the disease and the uncertainty surrounding Etep's long-term effectiveness (particularly in the 7+ age group), every clinical readout should be considered material for SRPT, especially because the FDA has told them how important the data will be for the upcoming AA. If they are truly under an embargo due to their presentation commitment at WMS in Oct, that's fine, but that does not prevent them from disclosing that the 144 week testing has been completed and there are no SAEs or significant changes in the boys' 6MWT results. I agree with the premise that if the results presented a material negative change in the clinical efficacy or safety, they would have to disclose that immediately, but the idea that we have to wait until Oct to get any official word from the company on the 144 week results is ridiculous.
jrrt - I'm going from the individual 6MWT data tables in the latest presentations - those show 6 patients in the treated group and only 4 patients in the placebo delayed group, so the twins must have been in the placebo delayed group.
The other aspect of this non-issue raised about the Willis twins is that if there were to be any of the patients in the trial that were expected to show some level of deterioration, it would be these two boys. It is clear from the rapid deterioration of their leg strength early in the trial (they were in the placebo-delayed arm and lost ambulation by week 36-48) that the existing damage to their muscles was greater than the other boys in the trial - why would this damage be limited to their leg muscles? They could also have significant damage in their arm muscles that doesn't present itself as clinically obvious as it did in their leg muscles w the loss of ambulation. As they age and their bones grow, does the remaining healthy arm muscle tissue grow normally and allow them maintain their function or is it too damaged to grow normally and keep up with the additional weight and length of their arms, hands, etc. and do they lose functionality?
IOW, it is ridiculous to expect that there are two distinct outcomes with DMD boys on Etep - retain full functionality and lose all functionality. There will naturally be a full range of potential outcomes, depending on when treatment starts, existing muscle damage, dosage, etc., etc. We can hope that all the boys in the Etep trial were started early enough to maintain the function that they started with as they age, but that probably will not be the case. The hope is that if you start them early enough, they will live the life of a Becker patient - that hope cannot be tested in the current trial and the only way to realize that hope is to get all Exon 51 DMD boys on Etep as soon as possible.
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.
You just don't get it, do you? You compare Etep's prospects to DVAX, who was seeking final approval for a vaccine Hep-B, for which there is already a safe, effective vaccine on the market. SRPT is seeking accelerated/conditional approval for a terminal illness that has no effective treatments - this only requires that the evidence show that Etep is "reasonably likely" to provide a clinical benefit, with verification coming from the pending Phase III trial. Do you really believe the experts would take the data generated to date and say it was not reasonably likely for Etep to be working?
The 144 and 168 week results would have show dramatic deterioration by some boys for the overall efficacy picture to become questionable. Some posters would have you believe that even one or two boys showing moderate deterioration would be enough to taint the results, even with the knowledge that at least 3 boys will most likely remain stable or improve vs the 120 week results. That is the wager being made right now - my money is on the side of the future results being good enough to maintain Etep's status as "reasonably likely" to show clinical benefit. Severe safety issues cropping up at this stage are extremely unlikely and with 3 moms touting "improvements" in their boy's physical capabilities, I believe the deck is stacked for solid results in the future 6MWT scores. Your posturing is based on nothing but speculation and invalid comparisons.
Duh - That is why the advisory committee will be so important - the experts will tell the FDA that it is "bloody obvious" that Etep works, just as they have been saying in other conferences. You can't even get your facts straight on DVAX - the vote was 13-1 in favor of DVAX for efficacy and 8-5 against approval for uncertain safety. Try again, sparky!
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.
No doubt - the CEO has options on over 2Million shares at an average exercise price of well under $5, so for him to plunk down $100K in cash when the share price is over $16 is meaningful. I'm guessing he sees the recent $60 target as feasible. There is a lot more to the OMER story than just Omidria - the value of the pipeline will play out well before the revenue from Omidria catches anyone's attention.
The only reason that RNA is fighting is because if they admit that their drug can't compete, they are essentially throwing the towel in on the entire platform. Their intended mechanism of action is the same as Etep, but their delivery vehicle is too toxic and presents the same issues for any target they go after. Throwing in the towel on Prosensa is essentially admitting the entire platform is worthless, which may be true, but they can drag it out and pay themselves healthy salaries along the way until the money runs out.
hw - why would the boy breaking his ankle require a disclosure - it did not material alter the results of the test and to the extent it did, it was easily explained. Unlike simp, I don't believe the maintenance of the statistically significant difference between the treated and placebo-delayed arms has any relevance past the initial 48-week study period, so there is nothing "material" that resulted from the boy breaking his ankle. If one or two of the boys suddenly lost ambulation or had SAE's, that in my mind would be material and need to be immediately disclosed.
"investors asked the CEO directly - it was personal" - where did you get that from? If that is true, why not disclose it in a press release - just as the announced the participation in the conference in a press release? Since JMP is a hi-profile conference, if CG couldn't make it, the company would typically send someone else in his place. My point is bad news has to be disclosed in a timely manner, but the one thing a company cannot and does not disclose is ongoing deal discussions. I'm not saying that is what is going on, but it is a more probably explanation than your delusional insights into the "complicated" data.
The reason for canceling the JMP conference is open to speculation, but the fact that they haven't disclosed anything yet, probably means it is potentially good news, rather than actual bad news. They have an obligation to disclose material facts in a timely manner - if the 144w data was factually bad, they don't have the option of sitting on it for an extended period of time. Potential good news, in the form of ongoing negotiations for a sale or venture, are not required to be disclosed until a transaction is consummated. If it was bad news, I think the bomb would have been dropped by now?
mis-stating again, simp - "one significant decliner, as there was a few tests ago"? Which patient was the "significant" decliner and at what week? Don't tell me you are referring to the boy who broke is ankle - I know you are an idiot, but that would put you in the realm of ret@rded. I'm not aware of anyone touting "wide scale" improvements - just people taking the parents accounts of boys showing improvement in their day-to-day activities and anticipating that may lead to improved 6MWT scores. You know, using facts and reason, something you have a hard time doing in your own life.
simp - I never said that the boys definitely improved their 144w 6MWT score, I said based on parent reports on how their boys were "improving" that it was "likely" they would show improved scores or at least show continued stability. You are the one referring to reports of "complicated" data without anything to support it.
Sorry - I misunderstood. I'm not aware of simp ever backing up any of his delusions with any objective evidence - besides, I can't imagine a parent posting bad news about their boy?
The best source is Terri Ellsworth's twitter page - in addition to updates on her boy Billy, she re-tweeted the story of Sawyer Joachim on 4/23 and generally re-tweets stories about how Max McNary is doing, from his mom Jenn.
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.
Two things - first, you completely misrepresent what Hoffman said in the interview, not that I care much about his opinion, but he spoke more about the manufacturing cost issues of PMO's than anything else. Stating that there are many unresolved issues about dystrophin measures (how to measure it, what levels are needed for clinical benefit, etc.) is nothing new or is it an issue exclusive to the Etep program (at least SRPT made a valid effort to measure dsytrophin in their trial, which RNA did not). Second, you're an idiot!