simp - you are forgetting that there are two meetings - they said there was a separate meeting in April to go over manufacturing issues. My guess is that the FDA will not give them "guidance" on an AA until they have a better understanding of whether they can get the manufacturing up to scale in order to support commercialization in 2014.
Well then their $52 price target is too low, because drisapersen is dead in the water - even if they could get it approved, why would any physician/parent choose it over the side effect profile of eteplirsen - and accelerated approval is a slam dunk.
I agree that is probably a long-term positive, but I'm not sure of your timeframe of "1-2 years out" to ramp up marketing for LUNA. In the press release they speak to how terminating the agreement with KCI will allow them to "accelerate the launch" and how the commercialization begins this month at the DFCon conference - based on those comments, I would expect they would have a full marketing launch in place by the end of the year?
Nice - many times these filings end up being option awards, but these are direct acquisitions - cash from their pockets. It's hard to predict when this stock breaks out above $5, but they have the cash to fund them past numerous milestones in both Fabry and Pompe, so the downside is limited and patience won't get punished with dilution.
Exactly - anybody with a child that has DMD probably already knows about eteplirsen and will be lining up at their doctors office demanding treatment as soon as the drug is available - the idea that you would need to make any kind of sales "calls" is just silly.
No sense in "selling out" until you have proof of concept of the drug behind you - take as much clinical risk out of the equation before you ask big pharma to value your company. I've listened to a couple calls/presentations by management and I don't recall hearing a management team so giddy over the results they are seeing with their drug. This reminds me of THLD - a unique mechanism of action against an unconventional tumor target with broad applicability (i.e. works in a number of different cancer types) - this has blockbuster written all over it!
fenix - thanks for the info on Fabry treatment and clinical symptoms that patients are dealing with. I wasn't trying to be pessimistic - I am long here and believe FOLD has a very good shot at accelerated approval, primarily because of the clinical history of treating patients for years and patients electing to stay on it, while the analysts on the call seem focused on how the trial stats and endpoints might be modified in the next phase in order to prevent another endpoint "failure".
jham - my reference to the analysts' views was not to reports that I have seen, but based on the content and tone of their questions during the conference call - they clearly view the 1st 6-month phase of the Phase III trial to be a failure and that unless the 12-month phase comes through with solid results, migalastat will have no chance of approval. Management, on the other hand, believes that the first phase showed solid results (because they dismiss the patients with low baseline readings as generating meaningless data) and that the 2nd phase will show continued/improved efficacy in the treated patients from the 1st phase and good efficacy from the crossover patients in the 2nd phase - they also imply with their comments that the accelerated/conditional approval rules will allow the FDA to be flexible in analyzing the data that comes from the trial. Given my understanding of the accelerated approval process, I don't believe management is over-stating the case - as the CEO stated, he "knows" the drug works, it is just a question of analyzing/presenting the data in a way that convinces the FDA.
fenix - you are making a leap of faith that the the patients that were enrolled as having "amenable" mutations in the initial enrollment analysis, but then were found to not have the right mutations (and so would not be expected to respond to migalastat) were in the treated arm of the study - if they were in the control arm (and didn't respond), taking them out would make the placebo response rate higher (and worse for a comparison). I'm actually surprised they disclosed this issue without having some detail behind it to discuss - they didn't even have the number of patients that fell into this non-amenable group, let alone what the breakdown was between the treated and control arms for the 6-month phase of the trial.
I listened to the call this morning and the thing that struck me is that there is a clear gulf between management's interpretation of the 6-month trial results and the analysts' view. The last analyst even came out and questioned what 12-month results would be needed to allow them to "continue the program" and implied the clinical results to-date did not show the drug works. While they responded to this implication somewhat forcefully, I doubt they convinced the skeptics. The CEO made the comment about "knowing" that migalastat is an effective treatment and alluded to the experience of the patients in the extension studies (roughly 20 in the Phase 2 study with many on the drug more than 5 years and 57 of the 60 patients in the Phase 3 study electing to continue taking migalastat after the end of the 12-month study, which ended in December). What I wish they would do, and something I e-mailed their investor relations department to request, is discuss in more detail what these patients in the extension studies are experiencing and what their doctors are seeing/measuring that has them convinced that the drug is effective - this information will be just as important, if not more, in their application for accelerated/conditional approval.
From what I have learned about the process from following SRPT (where the analysts have badgered them to death about the accelerated approval process), the FDA is supposed to provide official meeting minutes within 30 days of when they meet, and unless something unusual happens, FOLD should have enough guidance at that point to know what the prospects for accelerated approval are. It is interesting to contrast the comments by FOLD management in the calls and presentations, where they have pretty much said they will definitely be seeking accelerated approval (before they have the full data from their trial or have met with the Fed), versus SRPT, who will not comment on whether they will be seeking accelerated approval until after they meet with the Fed (sometime this quarter). Whether they are blowing smoke, or not, I think Fold management is highly confident that they have good enough data (certainly they have enough clean safety data) to file for an accelerated approval.
Later - the meeting in June will only give them the FDA's nod on whether an accelerated/conditional approval is feasible - assuming the FDA doesn't burst their bubble and tell them that an accelerated approval is not possible, they then have to file the application, which would take another 3 months or so to pull together, and the fastest they could get approval would be six months later ("priority review" provides for a 6-month PDUFA from acceptance of the application, instead of the normal 10-month timeline), so the earliest they could get approval would probably be 2nd quarter of 2014. The stock is trading as if mialastat is DOA at the FDA, so if they 12-month data is good (even if the low baseline patients continue to contribute noise to the results) and they get the nod to file for accelerated approval, the stock should recover over the summer. Even if the accelerated approval path is blocked, they have enough cash and other clinical milestones coming over the next year that I don't see a lot of downside from here?
Another key point - stability testing should not be a factor to delay approval, as they will have good stability data on small & mid batches and the drug is not expected to sit on the shelf for any extended period of time after launch.
You guys are looking at this through the lens of traditional approvals - i.e. whether designated clinical endpoints and statistical significance are met. What you have to focus on is that FOLD is seeking accelerated approval, where there is a lot of flexibility on the FDA's part to analyze small data sets and statistical significance is not the overriding factor. If you are familiar with SRPT, they are moving toward an accelerated approval based on a trial of 12 patients in muscular dystrophy. A patient advocacy group just had an FDA official participate in a discussion of how they approach the accelerated approval process and this official discussed how important "patient reported outcomes" are in the analysis - i.e. how has the drug changed the patients' day-to-day lives. Consider how many patients have elected to stay on this drug after the formal trials have ended - do you think the FDA is going to dismiss that fact and focus on a group of patients on placebo that have moved from 0.2 to 0.1 on their GL3 measurement?
I agree - the current price shows no value for the tubulysin program (blockbuster with a prostate cancer targeting agent) or the inflammation program (this will take longer to develop clinically, being chronic conditions, but the potential is enormous). While the overall market scares me, there are a number of small biotechs like ECYT that are just beginning to show their value - the next few years will be interesting.
fenix - look closely at the slide (#11) in the presentation - the median % reduction in placebo was only 6%, but the range was from a reduction of 58% to an increase of 49%, versus a median % reduction in the treated group of 41%, with a range of a reduction of 72% to an increase of 26%. This analysis, like the full primary endpoint analysis, is based on the full 60 patient population, so these wide ranges of results (% change) is most likely attributable to the same measurement issues they dealt with in the primary endpoint - e.g. a placebo patient that went from .2 to .1 would be a 50% reduction, but could simply be measurement noise. This is why in the end the FDA will toss out the patients with low baseline numbers - whether the cutoff is 0.3 or 0.2 probably won't matter, especially if the 12 month data shows consistent or improving results and the placebo patients (with baselines above 0.3) crossing over show similar reductions as the treated group at 6 months. I'll say it again, when you have 90%+ of patients voluntarily staying on the drug through multi-year extension studies (on the advice of their physicians), you have a drug that is effective and safe. Safety is a no brainer hear and efficacy is clear if you eliminate the noise - the FDA will and we will have a winner.
More like $2M (the venture fund he runs put bought roughly 1 million shares of the latest offering). He has had his hand in a number of winners and there are a number of other heavy hitters on the board, so you would think the stock would be holding on to the $2 price of the latest offering? They certainly have enough cash to cover all the marketing efforts over the next year, so maybe there just isn't any faith in the core technology? Will Galectin become part of the standard heart health narrative like LDL, HDL and triglycerides - maybe not until there is a drug/therapy that helps reduce galectin levels - what good is knowing your galectin levels are high if you don't know what you can do to control them?
Your numbers for the next year may be reasonable, but the real revenue/profit picture of this company won't be fully realized for another 3-5 years. There are so many growth drivers in the early stages that a 40% growth rate over the next couple of years is going to be dwarfed by the growth rate 3-5 years out. The adoption rate in their lead indication (breast reconstruction) from one market (open surgery) is still less than 15% - when you get 3-5 years out, you will have multiple indications from multiple markets (open, Firefly, PinPoint and Luna) driving growth, and while it may have taken 3+ years for the adoption rate in breast reconstruction to get where it is, the adoption rate for future indications/markets will be much quicker. The beauty of NVDQ's technology is that it clearly saves hospitals money (by reducing complication rates) and the equipment cost is relatively minor - contrast this with ISRG, whose daVinci equipment costs over $1M upfront and the per surgery accessories are much higher than Spy kits - meanwhile, clinicians are starting to doubt the value of daVinci procedures vs other minimally invasive methods.
The Citi presentation was the first where I have heard the CEO confidently speculate that the US revenue opportunity is $1B-$2B annually. If 3 years out the path to that $1B revenue run rate has been laid, the market will assign a 2-3 times multiple to that number, which would translate into a $50+ stock price. The wild card in the equation is whether they finally make an effort to market Spy to the rest of the world - hopefully that will be a 2014 initiative, after the PinPoint and Luna launches are behind them?
What a completely clueless analysis - "a small subset of the population with a drug that really isn't all that effective". First off, migalastat as a monotherapy is expected to cover have of the patient population and for those mutations not amenable to monotherapy (or the ~30% that may not respond to monotherapy and have to go to ERT), migalastat will be used in combination with ERT - in other words, milalastat has the potential to be used in the entire population of Fabry patients. Granted, many Fabry patients may never go on ERT, either because they don't have coverage to pay for it or they don't want to deal with the bi-weekly infusions, but the potential Fabry market for migalastat is larger than that for ERT alone. As evidenced by the percentage of patients that opt to stay on migalastat in the extension phases of the study, there is a clear patient need/demand for an oral drug to control this disease and potentially keep people from having to go on ERT. With respect to effectiveness, it is clear from the Phase II & III data that roughly 2/3rds of the sickest patients respond to the drug (i.e. have their GL3 reduced by 50%) - if you are looking at the measurement noise in the patients with baseline GL3 below 0.3 as a sign that the drug doesn't work, again you are clueless - that is like looking at a flu trial and saying patients with a baseline 1 degree fever did as well on placebo as Tylenol, because a chunk of the placebo patients had a 0.5 degree reduction in their fever from baseline - like a 0.5 degree change in fever can be attributed to normal fluctuations within a patient or measurement inaccuracies, a 0.1 change in GL3 has the same issues. Finally, when you say "the market is getting smaller", the exact opposite is true - this disease has been under-diagnosed and under-treated for years - the ability to diagnose the disease with genetic testing and the availability of an oral treatment will expand the Fabry market over the next decade.