endo - I think #4 is key - there were some "one-time" charges in the marketing expenses for Q2 and they expect them to be flat the rest of the year, even though revenues will be increasing dramatically.
GSA - We have a mixed report here, so I hope it provides some support for the share price - $15M of revenue for Q2 beats the analyst estimates (~$14M) for the quarter, but they revised revenue for the year down from $65M to $62.5M. On top of that, they missed on earnings - a loss of $0.22 (excluding the warrant value adjustment) vs analyst estimates for a loss of $0.17. Marketing costs are still increasing as fast as revenue, so they need to break that cycle. I hope Arun provides some upbeat "color" to the numbers, otherwise we could dip into the $10's?
hw - I think you are assuming too much ignorance, not only on the part of doctors, but on the part of parents. There will be clear clinical evidence with respect to safety and dystrophin production that will position Etep as the more preferred drug, so even the most clueless doctor will not be "persuaded" by an aggressive sales pitch from BMRN. I also do not believe that there is a large portion of DMD boys being treated by "primary care" doctors - even if they were, what sales force is going to be wasting their time on primary care physicians, without knowing whether that physician is treating a DMD boy - it's not as if there is a list of them? Finally, you are dismissing the impact that social media will have on both parents and doctors - thus far, even with the limited number of boys on Etep, the parents have created a buzz in the DMD community about the impact that Etep has had on their boys. Not that I have searched extensively for similar stories about Drisa, but there doesn't seem to be any. By the time Etep is approved early next year, the boys in the confirmatory trial will be on treatment long enough for their stories to add to the buzz - we're already starting to see it. Do you really think a parent that pushes their doctor to get their boy on Etep is going to be persuaded to go for Drisa, instead? Either drug is going to priced at a level that no family could afford without insurance, so pricing is really going to be an issue the insurance companies will have to deal with - not parents and doctors.
The nice thing about some of potential pipeline indications is that the clinical proof of efficacy will be relatively simple and quick. Testing for the production and levels of a missing enzyme is an easy proof. I'm sure the FDA will likely want to show that the enzyme functions properly, as well, but it won't take 3+ years to do that.
Your negative point about needing to beat out Abraxane's 2.1 mo survival advantage over Gem alone hi-lites my point. Technically, THLD has a SPA that theoretically guarantees approval as long as the OS endpoint is met, regardless of whether it beats the 2.1 Abraxane advantage. At the same time, however, the company has started a combo trial of TH-302+Gem+Abraxane, in the expectation that whatever benefit over Gem realized will also be realized on top of Abraxane's benefit. In theory, it makes sense, given that Abraxane is not targeting the hypoxic regions that TH-302 is targeting? The question then becomes does the company have to do combo studies with every new drug that gets approved and given that so many of the new therapies are targeted/personalized, is that really a feasible prospect?
I was hoping STS was the more probable winner of the two Phase III trials - what odds are you giving the pancreatic trial? Regardless of whether the pancreatic trial is a success, it seems that the treatment landscape is changing more rapidly there than in STS. Ultimately, I believe the hypoxic-targeted approach will provide beneficial with most other agents in combination, but it may be hard to keep up with all the different agents that get approved over the next decade? The safety profile of TH-302 should pave the way for doctors to use it in combination more freely in an off-label setting, but who knows?
ru - once again, your argument runs counter to the context of Etep's worthiness of AA. The AA regs purposely provide the regulators the flexibility to consider "all of the available data" because with rare diseases, the trials may not be able to generate robust statistical evidence with the smaller patient populations and/or the short-term clinical evidence may not provide a clear picture of the long-term clinical benefit. Both of these issues are in play with Etep - it has become clear that the 6WMT is fraught with limitations in a population of adolescent boys, so even if the n was large enough, a statistically significant benefit would be difficult to achieve. If you want to rely on walking ability as the sole data point for approval, you would probably have to run a 5-7 year trial on boys starting at ages no more than 5-6. You have argued for dismissing the dystrophin data and ignoring any "subjective" assessments by the parents or doctors, but this type of evidence is exactly what the AA regs allow, while longer term clinical trials generate the statistically significant evidence you are obsessed with.
winter - You are so clueless it is painful. "One person's experience"? How many anecdotes of children gaining strength or regaining function that had been previously lost do you have to hear? As the parents have pointed out repeatedly, DMD is universally all about the continuous loss of strength and function - there are no cases of boys getting stronger/regaining function, let alone stabilizing. You can argue all you want that this anecdotal "evidence" may be meaningless to the FDA (in contrast to their declaration that it is an important part of the review process), but to dismiss all that the parents' have shared about their boys on Etep as "one person's experience" is truly ignorant, particularly in light of dystrophin production evidence.
pearsby - I didn't miss your point - your point is invalid - in the end, the better drug will be an easy choice for parents. Whether Drisa has a 2-month lead or 12-month lead is meaningless in the long run - parents will either wait for Etep (knowing that Drisa is toxic and may not work) or switch over to Etep when it becomes available. Etep will have a label that shows clinical evidence of dystrophin production and no safety warnings - Drisa will have "black box" warnings for liver toxicity and no evidence of dystrophin production - what doctor, let alone parent, will choose Drisa over Etep.
How clueless can you be? In the world of DEFINITE vs MAYBE, Drisa is definitely is not safe, with a high percentage of patients experiencing AEs, and maybe is not effective, with a failed Phase III trial based on 6MWT and no dystrophin data. In contrast, Etep is definitely safe, with 100% of patients showing no AE's (including those in the confirmatory trial) and definitely produces dystrophin, with 100% of patients showing evidence of dystrophin production. If the original dystrophin data was invalidated by the re-reads or the 4th biopsies, it would have to be disclosed by now, so we no that is not the case. Parents have an easy choice - they will flock to the drug proven to be safe and to proven to produce dystrophin - Drisa has done neither.
immediate - you are dead wrong when you indicate the 4th biopsy results will be a "minor addition" to the NDA. The 4th biopsy results are significant because they will counteract any questions that may arise from the 6MWT data. As has been discussed previously, there is a contingent of ignorance out there that believes if Etep was working that there would be no declines in 6MWT performance for the 10 boys. The 192wk data will likely show further declines and raise ignorant questions about whether there is enough dystrophin being produced to be effective or perhaps the levels measured at wk 48 are not holding up in the long term. The 4th biopsy will help to counterbalance these questions and reinforce long-term effectiveness of the treatment.
mauouo - You've answered your own concern when you say it "seems management is very confident". Everything they are doing with respect to filing, hiring, financing, etc. indicates that they feel very good about the hand they are holding, which they have yet to reveal. When the dystrophin re-reads and 4th biopsy figures are revealed, it will all make sense. The FDA challenged them with their ridiculous accusation of "marked disparities" in the measurement of dystrophin last October and now the company has the data to put the FDA in its place - they also know Biomarin has no comparable data.
Accepting a filing is simply acknowledging that all the necessary components of the filing are complete - it means nothing regarding the substance of those components or is any indication the FDA is acknowledging the filing supports efficacy or safety. Most companies wouldn't file a NDA based on a failed Phase III trial not because they didn't think the filing would be accepted, but because it would have little chance of approval and a waste of company resources. Acceptance of the filing is a non-event.
I think the binary event will be the Advisory Committee, which hopefully be early Q4 at the latest? I doubt the FDA decision will come through before the end of the year, despite the fact that they have had access to much of the data for months/years and with the size of the trial, the volume of data is limited.
They haven't announced a specific date, but have spoke to it in their last several presentations and that it will be in the 3rd quarter, after the data is unblinded from their Phase 2a trial.
Do people think they "need" the analyst day to spin the data because it is still not definitive or will it be an "in your face" presentation that will overwhelm all the doubters with clearly positive data from the multiple studies? They have spoken about bringing "key opinion leaders" into the presentation - to me that sounds like they are looking to say "you don't have to believe us" about the data, because they are not sure how it will be received? At the core, they have acknowledged from the beginning that they aren't sure what it will take to create a "functional cure" in HBV - they are blazing a new treatment trail - so, regardless of where the numbers fall out, I guess it will still take a long-term, pivotal trial to really generate "proof of concept". Either way, with the other programs progressing nicely, ARWR seems way undervalued?
I love it - the guy is arguing that a kid on Etep would "look funny in school" as a competitive advantage to Drisa. Beyond on how stupid that statement is on so many levels, it won't be the "kid" who will be making the decision on what drug to use - it will be his doctor and parents. The safety profile of Etep alone is enough to push the decision in Etep's favor, but when it is combined with Etep's clinical proof of dystrophin production (when Drisa has no meaningful dystrophin data from its late stage trials), Drisa won't even be part of the conversation between parents and doctors.
He has been at the helm for 15 years now and has struck out on every major milestone. The only thing he has been successful at is dilutive financings and getting his comp raised. His cash comp last year (salary + bonus) was $821K - I'm guessing he has pulled out close to $10M out of this company in the last 15 years, while shareholders are left with nothing. Good work if you can get it!
Doesn't matter when Drisa hits the shelves - Etep will be the drug of choice by both parents and physicians. In the unlikely event Drisa gets approved before Etep, you will probably have parents wait until Etep is available, instead of starting their kids on the toxic Drisa and having to switch later.