dawg - exactly, that is one of the things they spoke about in the July 2013 presentation - when asked by an analyst about the enrollment rate (did they add sites, competing trials, etc.), the CEO mentioned that the their VP of Clinical Operations (who was on the call) was grinning ear-to-ear about how strong the enrollment was. The issue of docs seeing meaningful benefit is even more relevant in this trial, because after the patients receive the max 6 cycles of dox (over the first four months), then the TH-302 arm has the option of staying on maintenance therapy with TH-302 alone - in the Phase II trial, this extension period generated additional responses with much less toxicity than the combo therapy. So, no doubt docs are getting a clear picture of the benefits of TH-302 and that influenced the enrollment rate toward the back half of the trial.
I agree w nurib - the worst case scenario is that they simply continue trial to the full OS measurement next year, but it is probably not a slam dunk that they will stop the trial early due to statistically significant results.
It has been so long since I focused on this trial that I went back and listened to their Jul 2013 presentation, when they modified the trial to add an extra 170 patients. Their caution was due to a single EROTC trial that resulted in median survival for dox-only of 12.8 months, but that trial excluded patients over 60, whereas both the Phase II and III trials for TH-302 have ~ one-third of the patients over 60. They noted that historically, dox-only typically generates MOS of 8-12 months and they were not aware of any changes to the standard of care of STS that would have increased that over the past couple of years.
There are certainly reasons to be hopeful for an early stop to the trial - the Phase II generated a MOS of 21 months and they probably only need to get to 18 months for early stoppage. Also, they had targeted at YE 2013 that the interim 235 "events" to take place by "mid-2014" and we have certainly been delayed meaningfully from that target. Then again, I've seen too many cases of "delayed" event targets that have crashed and burned to view that as a infallible sign.
Watched the video and the striking thing is that they said he was only diagnosed with ALS a year ago, so he was obviously progressing very rapidly. He states in the video that he has experienced improvements, but I assume when you are progressing as rapidly as he was, it is like trying to stop a freight train - minor improvements vs continued rapid decline could be very meaningful? Seems like ALS has a lot of different flavors and it will be hard to assess what actually qualifies as "clinical benefit"?
They have back to back robo-reports, the first saying the stock is a strong sell, because of earnings estimate changes (for a development stage biotech w no product revenues) and the next one hi-liting that the stock just jumped 10% in one day. I suppose they make money off of these worthless "reports" because there are ads tied to them, but they can't be attracting any clients with this kind of nonsense analysis.
endo - you just confirmed what I have been harping about - Arun isn't "methodical" - he is missing opportunities. When was the last time you heard of a company getting regulatory approval in a foreign country without already having a marketing partner lined up? They are dropping the ball here and the revenue growth is suffering - that is why investors are bailing.
himmel - you're not "throwing water on the fire" here - there never was a fire, just misguided speculation. Every point you made is perfectly rational, unlike the pointless pumping making Ebola out to be some great opportunity that would change the company's fortunes - it isn't. Even if sending doses to the jungle worked flawlessly and cured 100% of the patients, Ebola is not a money-making market - there is no system in place to pay SRPT or any other company what it would cost to produce the drugs.
If curing sick,dying people from Africa were a money-making proposition, you would see billions of dollars of sales for treatments in malaria, TB, etc. being generated - there isn't, because Africa can't afford to pay for them.
simp - on what "earthly" logic would providing SRPT's drug "help the containment effort"? The reason these countries can't contain the outbreak is because they have 3rd world healthcare facilities - they have trouble identifying who has the disease and getting them quarantined and handled properly. How is providing SRPT's drug going to change that equation? Even if you assumed that they had the capacity to utilize the drug effectively (i.e. dose it properly to patients that aren't already too far advanced), treating and saving patients is not going to control the outbreak. Give it a rest - Ebola is nothing but a potential distraction for this company.
More likely it will be used off-label with the Fabry ERT's - the company was moving down the road toward doing a combination study, before they shifted gears and decided to develop their own ERT, which won't hit the market for at least several years, so docs may want to use Migalistat with existing ERT's to enhance effectiveness and reduce immune response issues.
What "work" from Zach's have you ever found respectable. They issue ridiculous analyses of earnings estimate changes for development stage biotechs and the few qualitative analyses they provide on biotech pipelines and clinical prospects are typically thin and worthless. I can't imagine anyone pays attention to their releases and am baffled how they could make any money at what they do?
"weren't that conclusive" - positive results for both endpoints required a 50% overlap of the confidence intervals between the two groups - both endpoints achieved 100% overlap of the confidence intervals. 46 of the 48 patients that completed the trial elected to stay on the drug during the voluntary extension phase. What exactly is inconclusive, or is it that you don't understand the meaning of the word? Idiot!
Thanks for the link. Does anyone know whether Ted only participated in the earlier trial or did he also get a 2nd round of stem cells in the current trial?
No doubt, with their chaperone technology and their next generation enzymes, they are going to own the Fabry and Pompe treatment markets within five years - that equates to a multi-billion market cap by then, so the current share price is a bargain.
The initial results from the "011" study did not meet the pre-specified endpoint, which in retrospect was a flawed measurement. The original endpoint was whether the patient generated a 50% reduction in GL3 and an unusually high percentage of the placebo patients achieved this, because many of them had baseline GL3 readings of 0.3 and below, while the test can produce measurement noise of 0.1, so a patient with a baseline reading of 0.2 and post-treatment reading of 0.1 counted as a "responder", the same as a patient who went from 0.6 to 0.2. They addressed the measurement noise in the second stage of the "011" trial and the results were overwhelmingly positive, just as yesterday's results in the "012" study. The proof in the pudding is the fact that over 90% of the patients who have access to migalistat through these trials elect to stay on the drug into the long-term extension phases of the studies. The drug works - there is no issue regarding that. The question is what the market opportunity is and when it will be approved in the US.
endo - nobody on this board is arguing against the obvious clinical benefit that the various Spy equipment provides - there is no doubt in my mind that over the next 10 years, Spy will become SOC in numerous indications. The issue is how long it takes to get there - having a clinical study that demonstrates irrefutable clinical benefit is not enough - if it was, they would already have captured the markets in colectomy and breast reconstruction. Clinical studies are fine, but you need to get equipment placed and doctors trained and Arun isn't moving aggressively enough to make that happen - if he was, we wouldn't be wringing our hands over whether Q3 revenue growth is going to be 30% or 40%.
I was naive enough when I first invested in this company 5+ years ago that they could operate with the "field of dreams" strategy - build it and they will come. I thought the technology was so compelling that getting a few pieces of equipment into the leading hospitals and having the "thought leaders" talk it up a bit was all you needed for the rest of the medical system to beat a path to your door. That is obviously not the case and the breadth of indications available to be handled by Spy requires a huge marketing organization to make SOC happen - if you believe Arun can build it from the ground up, you are kidding yourself.
grey - agree with every point you made, although I never suggested they pursue the remaining part of the Ebola trials - unless, of course, the DoD resurrects their contract and pays them to do so, which seems unlikely.
BTW - I was looking back at the year-end press release (just 6 moths ago) and one of the "key accomplishments" for 2013 was the "appointment of a highly capable network of distributors in the Asian markets". Whatever the heck that means, it certainly hasn't gone anywhere the last six months and is just another example of Arun throwing around nuggets of opportunities or accomplishments that are meaningless. You give him too much credit.
I would take $20+ today - unless Arun makes some serious changes to get revenue growing, I don't think we will see that number for another 3+ years.
hwsimp - even if your scenario plays out (Ebola gets out of hand and govt contracts to build a stockpile), which I think has as much chance as winning the lottery, there is no guarantee the contract would go to SRPT and the "stockpile" would be limited and a one-time event. Just like in Africa, the emergency money should and would go toward containment - controlling the spread is the only way to defeat it - treating victims is secondary. Worst-case nightmare is dozens of westerners become infected - are they going to stockpile 100,000 doses under that scenario - no way.
That's a more intelligent post than most of the postings regarding Ebola. BTW, why do people say "tuna fish" - is there another kind of tuna - you don't say "salmon fish" or "walley fish"? Just sayin'!
Whether DOD changes their mind or not is meaningless - by the time they shift gears on a DoD contract, you'll be two years down the road and this Ebola scare will be a distant memory. Show me the slide that says who is going to pay for the drug and at what price!