The amount of misinformation on this board is stunning. It is very clear that that vast majority of people posting don't have any idea of how the FDA approval process works.
Before I begin, I will say I have no particular insight into Dendreon, or Provenge beyond what is publicly available. I am merely an investor in a very promising company. However, I have considerable background in the pharma industry in both manufacturing, research and submission processes.
First of all, the FDA can NOT simply approve Provenge based on the data as presented to the AUA. It must be submitted to the FDA as part of a NDA/BLA. Nothing else really matters, regardless of where it is presented, only what is part of the submission. The data recently presented has not been submitted to the FDA yet.
Normal submission process takes a minimum of 10 months from the date an NDA or BLA is accepted for review. In the case of Dendreon it will be a BLA - Biologics License Application. The differentiator is generally whether a composition contains live cells or not. The processes used to be very different but they are fairly similar these days.
I suspect that Dendreon will apply for Fast Track status and may have already done so previously. This should not be confused with Accelerated Review though most are often granted such if they obtain Fast Track. With Fast Track portions of the application can be submitted separately theoretically speeding up the process. Fast Track Status is not an indication that the FDA sees the drug as approvable. The legislation the governs Fast Track is designed "to facilitate the development and expedite review of drugs and biologics intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs." If a drug is targeted to serious or life threatening disease or conditions it will get Fast Track status as it demonstrates "potential" to the FDA. It absolutely does not mean that the quality of the submission is high or that there is a strong possibility of approval.
Accelerated Review often goes hand in hand with Fast Track. This is designed to speed up the approval process. Normal approval process is 10 months from the date of the LAST piece of the application is sent to the FDA. Accelerated Review takes approximately 6 months from the date of the LAST piece of the submission to the FDA. The review process can NOT begin until the submission is complete.
Acceptance for Review is where the FDA examines the submission for completeness. This process is supposed to take 60 days. This has nothing do to with the actual quality of the submission or the approvability of the drug, only that the application has been completed correctly. After the 60 day mark the FDA will let the submitter know whether accelerated review or not will be granted.
Since Dendreon has not submitted a BLA, this process has not begun. The earliest Provenge can be approved for marketing is in mid 2010 provided Dendreon completes their submission by 4Q as planned. There is absolutely no way Provenge will be approved in 2009.
Dendreon must also qualify it's manufacturing, and packaging facilities. This is a separate task and not insignificant.
Complicating things a little is that Dendreon received an "approvable" letter for Provenge in 2007. On the surface it sounds good but it's not. It almost certainly means the FDA requires more information, trials, what have you. Which is exactly what happened with Provenge. Approvable letters are not good news. Certainly better than not approvable of course.
Some of the above process is already complete though I do not know the extent of the rework required. Hopefully that provides some insight into the FDA drug approval process and timelines.
Well written...but you forgot one thing: The actual administration (Obama's) have a focus on any kind of development of this kind that can improve life...He specifically said that there was now a fast track for those companies coming up with solutions.
Now as you mentionned and know...THey have work very closely with FDA guidelines...to ensure that there will not a second 2007....
I agree that in normal situations the FDA process that you are describing is very very acurate...however this is not a normal situation...plus I could add that there will be a lot of pressure from patients and doctors for FDA to go faster...since they just proved again and even in a better way their claims.
Thanks for posting..very instructive.
Great Post Greg, Thanks. Based on your experience, is there any chance that a Big Pharma may buy DNDN before the FDA approval or even FDA filing? Seems like noone will take the risk until approval is obtained, even though it's nearly 100% guaranteed.
Also, when do the Companies like DNDN sign up a partner? Is it before the filing or approval?
thanks very much
The BLA was filed over 2 years ago, the current data will be submitted under that BLA. They have had fast track status since 2007, the current data is in answer to the approvable letter, which asked for a larger sampling as its primary reason for being issued. They are under a SPA with fast track status. Pardon me for saying so, but if you know so much about the process - which you seem to - and are really an investor in DNDN, you really should have known that a lot of these hurdles have already been crossed before investing. JMHO, and to each his own DD. There were a couple of manufacturing questions that have already been substantially addressed during the trial process, and have been fine tuned. They will be working on their AMENDED BLA through early Q4, and expect an answer from the FDA in very early to mid 2010. That's the scoop - but thanks for providing what is at least a thoughtful post in a desert of misinformation.
A BLA has already been submittted, hence the approvable letter in 2007. An amended BLA needs to be filed; however, the FDA can approve on their own sua sponte. Procedurally, the FDA has everything it needs, for a conditional approval. The SPA is a contract with the FDA - if the conditions are met than approval will follow. The FDA is involved in litigation concerning the denial in 2007. The SPA wanted a larger patient pool, their reason for denial in 2007 is moot. The FDA frequently grants early approval on drugs that significantly increase the standard of care, Erbitux and Taxotere come to mind. A 4.1 month increase in survival, with NO side effects is a SIGNIFICANT increase in the standard of care the best available is 2.5 months. I for one am checking the federal register daily. This is because a settlement in the provenge litigation could be negotiated between counsel and not announced formally, I will also be looking for a dismissal of the carefirst lit for a tip of the hand, but i suspect will hear it from carefirst "first"
Code of Federal Regulations
Title 21: Food and Drugs
PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG
Subpart D—FDA Action on Applications and Abbreviated Applications
§ 314.160 Approval of an application or abbreviated application for which approval was previously refused, suspended, or withdrawn.
Upon the Food and Drug Administration's own initiative or upon request of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in theFederal Registerannouncing the approval.
You clearly have math problems.
By 4Q does not mean Dec 31. In all likelihood it means by Oct 1. Therefore if 6mo of accelerated review is granted, than PDUFA date could be as early as March 31. However, since FDA already erroneously delayed provenge since 2007, there might be an additional impetus to approve it early. I give it 10-15% bY Dec 31 and 70-75% by March 31, 210.
However, for all I know FDA could grant an immediate approval for the compassionate use.
contingency, and compassionate usage is what the FDA may be pressured to do. They have already granted "limited" use to select studies of patients now. With this "NEW" FDA in place (and hopefully LESS back-door pandering along with it) I see something done in WEEKS (not months).
The FDA will not give immediate approval. Not gonna happen. No way. It would be nice though. The FDA will review the data and the BLA.
The PDUFA date maybe March of 2010, it all depends on how fast DNDN get's their submission in order. I only know what everyone else does and that is 4Q 09. If all goes well, and I have no reason to expect that it won't then there will be 6 months between completion of the submission and final approval.
Good effort to educate the collective. Couple of points to include. This would be an amendment to an accepted BLA (from 2007), and because it is under a SPA (Special Protocol Assessment)--which stipulated what would be required for approval in the approvable letter--that further accelerates what needs to be added to the filing. It is not a new submission. They are already Fast-Tracked (original BLA status doesn't change post approvable letter). In a perfect world, amendment is submitted in early Q4 (October), and reviewed/approved prior to the end of Q4. But either way the timing for submission approval is much shorter than if they were starting from zero.
I've been in drug development for 25 years, this is a landmark collection of data. Men are still alive that were "dead men walking" seven years ago that received this therapy in the early stages of the clinical trials. That's huge!
Just realized I'm just parroting you, Shasta.....should have read through the whole thread 1st! Thanks for the good info for everyone....there is still intelligent life on the Yahoo boards, it seems...
Yes, you are correct regarding the SPA and the BLA. DNDN is not starting from scratch. I still don't see any approval before the end of 09. Again, I'd love to be wrong on this.
Part of my original post was simply to provide clarity on the whole approval process.
well what if they already went thru all that in 2007!!! and this is a spa agreement hit the numbers and you are approved, all that has to be done is ammend the current bla that is already on file with the FDA and fast tracked to approval. You make a valid post but you forgot DNDN already submitted BLA 2 years ago.
Since there are more data points, the FDA will need to see the raw data for the new results. They examine individual patient records, trial protocols, IRB results, everything. They will do their own statistical analysis, usually in a more adversarial fashion (i.e. less optimistic assumptions & methods). And they will scrutinize the procedures to make sure that all the criteria for the SPA have been actually followed.
Given that some of the work has been done already, e.g. describing preclinical results & toxicology & pharmacology, it is less work than a totally new application.
It is a major amendment to the BLA, as they are submitted new data from a major trial. There is still an enormous amount of paperwork, unfortuantely.
I think it's very probable that approval will eventually granted.
No I didn't forget that DNDN already submitted a BLA in 2007. They received an approvable letter based upon the submission.
Just because you are given an SPA, and hit your numbers, based upon an approvable letter doesn't mean "you are all approved". It just doesn't work that way. It would be nice, but that's just not the way it works. Fast Track is a different process than Accelerated Review. What DNDN needs is accelerated review.
You can hope all you wish but I do not see how it is possible for Provenge to be approved for marketing by mid 2010 based upon currently known information. I'd love for Provenge to be marketable by the end of 2009 as well but it just doesn't seem possible.
cap you are correct. seems people have forgotten a lot of what happenen. Remember that DNDN negotiated a threshold.....22% which relates not so much to survival but too the realability of the data. The FDA has already agreed to approval, they just need to examine the data for accuraccy and statistical errors.
Finding none this IS approved.
the original poster is correct also insofar as the manufacturing process for commercialization. this may prove more challenging. since each dose is custom made doing this at a commerical level as apposed too limited production in a trial is quite different.
remember back in 2007, the FDA did an inspection of the plant and had some "issues" at that time. subsequent pr indicated they were solved BUT we have no independant confirmation.
if no news happens over the next four months this will be under constant pressure with missinformation and stockholder fatigue will set in and this will be walked down to the mid teens. puts are still a little expensive for me so wont be buying, but i will probably add to my possition substantially at anything below 15.
What if DNDN already started that process in 2007?/ Could it mean we are in the last stages? And now that they say Provenge is "effective" does that not mean anything to this equation?
I was just going to post this. Thanks. The process this time should be more streamlined since the data is simply a response for additional info. I am no expert, but I am sure DNDN does not have to go through the entire process over again.
That said it will still be several months before we know anything.