The laughable thing is how all these critics try to poke holes or find imperfections in the data, as if the perfect placebo group or comparison exists and SRPT just failed to design the trial properly or they are cherry picking the data. The reality is that you could never find two DMD boys (let alone 12 or more) that are at the exact same stage of the disease at baseline - there is no way to definitively measure that. Add to that the variability in disease progression and the variability of how the boys grow in height and weight over the course of a year (let alone 3+), and the 6MWT becomes less than "perfect" as a clinical efficacy measurement.
SRPT, knowing through dystrophin production and the reports from parents & doctors that Etep works, is criticized for providing all their data and trying to make sense of it. Meanwhile, BMRN has admittedly cherry-picked 6MWT data from their failed Phase III trial, has provided no dystrophin or other data, but escapes criticism and has the pundits declaring they have an equal chance at approval as SRPT. What a joke!
Does anybody know what the longest period of time that any Drisa patient has been on the drug? I listened to BMRN's most recent earnings call and when asked whether they would be providing any additional data prior to the AdCom meeting or PDUFA date, they said no - their filing will be limited to what they provided the FDA back in April. Do they have any extension studies ongoing that would show long-term safety issues or are they just hiding that data? Seems to me at the very least the FDA would want to see longer-term safety issue for a drug that is to be taken for life.
"if the drug fails"? The drug has proven its worth in the clinic - patients in the extension trial have been on the drug for up to 9 years - there is plenty of data to show it is effective and a lot safer than ERT. It is situations like this that make me believe that there are pressures/conflicts within the FDA to keep the gravy train going for the big pharma players with ERT drugs. As one of the analysts spoke to on the call, when did gastrointestinal issues become a focal point for approval of a Fabry drug - it certainly isn't one of the major morbidity risk factors for Fabry patients and it could certainly be studied in the context of a confirmatory study. This smells like delay tactics on the part of the FDA and it certainly isn't with patient benefit in mind?
Yeah - basmati rice is a new, never before seen product that will fly off the shelves as fast as they package it! This is a basic food staple that is available everywhere and not many Americans are going to suddenly start craving basmati rice, just because whole foods carries it. Get a grip!
Exactly what data has he not "exposed"? The idea that the FDA may want more data is not a revelation - they were planning on filing for conditional/accelerated approval, which requires a confirmatory study - the FDA could demand whatever data they want in that confirmatory study.
But I didn't pay attention. I noted on this board that the Sep 15th press release about their Pre-NDA meeting spoke to the analysis of gastrointestinal symptoms in a Phase IV study - these symptoms were never even referenced in an earlier studies, so you knew the FDA was asking for additional data. Also, if you read the Sep 30th press release about the closing of Scioderm, it conspicuously has no reference at all to the regulatory path of Migalistat in the US, while all the other programs and progress was hi-lited. In the end, this may be nothing more than a few month delay - they were planning on doing a confirmatory study, anyway - and they have the cash to get through the next 18 months. If they get approval in the EU and scioderm progresses, we'll be back above $10 within 6 months. The worst part is they didn't have the balls to hold a conference call to provide some color/context on the situation.
I agree - the press release is so poorly worded, you get the sense they are trying to hide something? The sense is not that Arthrex approached NVDQ and needed SPY to be competitive, but the other way around? After all the hype about kicking LifeCell to the curb and how they were in control of marketing their full product spectrum and all the related synergies, they enter a marketing deal, but provide no details on terms or have a conference call to discuss it?
The first analyst question regarding dystrophin measures led to a long-winded answer from Steve Wilton, but at one point he referred to pre-clinical studies (one in 2006 and another in 2009) that showed that Etep's PMO delivery mechanism is "10-times better" at exon skipping and dystrophin production than the oglio delivery - not sure if it specifically relates to Drisa's delivery technology, but he was pretty adamant that the dystrophin measures from the current Etep trial clearly show that dystrophin is being produced post-treatment.
The Needham analyst (Chad Messer is it?) has to be the most brain-dead analyst I have ever heard. Again, he fixated on the idea of a correlation between the dystrophin measures and the 6MWT or other performance measures. After Mercuri explained that even in Becker's patients (where there is significantly more dystrophin and performance data available) it is impossible to generate a linear correlation between dystrophin and 6MWT because there are so many other more important factors involved (e.g. degree of muscle deterioration, height, weight, etc.), the guy retorts that maybe when they "become more sophisticated" in their research they will be able to find a correlation - what a tool! This led to one of the other panelists to note that the dystrophin measures are isolated from a small muscle sample and may not represent "body-wide" levels or the levels in the muscles being tested in the performance measures. IOW, as has been discussed ad nauseam on this board, it is simply moronic to even think that there would be a correlation between dystrophin measures and 6MWT (particularly in boys older than 7) - the fact that Chad (a PhD who makes his living analyzing biotech companies) can't get that through his thick skull is just laughable.
The safety profile of PMO puts SRPT in a different class than the other RNAi companies - I'm not aware of any of them that have this clean of a safety profile. It's one thing to have safety issues if you are treating cancer or some targeted acute condition, but when you are dealing with a life-long, chronic treatment.... SRPT will be able to enter indications/markets the other RNAi companies can't touch.
The patent relates to the use of oglionucleotides - SRPT uses PMO's - why is this even considered an issue?
Hopefully, the data won't need much explanation. Ideally, the dystrophin re-reads and the 4th biopsy will be conclusive and consistent among the 12 boys and there won't be a need to spin or rationalize the results. While you would think the fact that the 10 ambulatory boys are still "on their feet" (presumably meaning they all completed the 6MWT) at 192 weeks would be conclusive evidence of clinical effect, I think there is still a major fraction of the "market" that believes any continued deterioration in 6MWT distances casts a cloud of doubt over the efficacy, regardless of what the natural history would predict.
The prospects of any "real big" news regarding FDA approval or company purchase are negligible - you don't need a an expert panel to discuss those issues and the company has been very prudent not to provide any speculation on what the FDA might do. With respect to data from the confirmatory trial, you can only expect safety at this stage - the anecdotal tales from parents of perceived benefit are nice, but the company is not going to speak to those and will not discuss clinical efficacy endpoints until data is available for the entire trial, which won't be for another year+.
How are you coming up with your "EV"s for the two indications? My guess is that you have completely ignored the fact that the drug is partnered with Merck - THLD effectively owns only half the economic value of the drug going forward. Beyond that, while I hope your probability of success in the PC market is on target, the PC market is attracting a lot of new drugs, so it will either be more competitive or slower uptake of TH-302, as they will have to test the feasibility of using it in combination with new treatments as they emerge - they are already doing studies to see if it is safe and effective in combo with Gem+Avastin.
Ultimately, the real value of TH-302 lies beyond STS and PC - if it proves successful in some larger indications (e.g. NSCLC) and/or proves to provide a clear boost to the angiogensis inhibitors like Avastin. Hopefully, the approval in STS and/or PC will lead to significant off-label use and studies in other indications.
end - From what I can tell, you were expecting to hear about "some FCs" from the latter cohorts and since you didn't get it, you are bashing all the data. The idea that they would be able to generate FCs from single-dose cohorts is so moronic that I can't even believe you would admit to thinking that - it certainly taints the rest of your opinions.
The FDA's "processes" are a joke. Think about it - Etep is supposedly fast-tracked under the FDASIA rules and they are dealing with data from 12 boys - it should not take years to "process". Thus far, they have hid behind their process and given flimsy rational for their decisions to delay. Obviously, public pressure has had little effect on their process.
I think part of the problem is that the data/results they are touting sound different than what you see from the multi-billion $ valuations coming from the HepC market - there the key data point seems to be SVR (i,.e. Sustained Viral Response). Here they are talking knockdown (which presumably will be sustained under a multi-dose regime?) of antigen levels (is this the same as a full "viral response"?). The fact that the "experts" in the HepB field have yet to define what will constitute a Functional Cure also dampens the results. If they had come out and said they had "cured" some of the chimps with ARC-520 and were generating similar early KD results in the clinical trials, I think we would be in the $20's. Instead, the most compelling chimp result seems to be one that had an "immune reactivation" - is that the same thing as a cure? Different lingo leads to confusion.
I'm as hopeful as the next investor, but I think it is a stretch to assume they can go from an open label "proof of concept" trial straight to Phase III - they would most likely do a smaller controlled study at whatever dosing/combination flushes out of the Monarc trial. Either way, I think their strategy is to partner ARC-520 - taking it all the way through Phase III will require resources they do not presently have?
"Hype" - what hype? The company isn't hyping anything - is there a market "buzz" out there? Either way, your $4.30 target is laughable - $6.30 is more likely!
Hey mister - we're getting close to that 3% swing you were looking for - oh, that's right, you were waiting for it to go down 3%+ before getting back in. I hope you'll still be waiting when the stock hits $50.
I haven't spent much time monitoring RNA/BRMN's communications over the past couple of years - have they ever disclosed how many patients continued on into the extension phase and/or provided any data from that study?