Paradigmers, on the back of some super posts by people that have personally experienced the magic of PPS, tonight let me post on the possibility of a certain designation known as 'Break Through'.
On the 9th of August Gan Gans wrote that the FDA could possibly give us a Breakthrough designation.
Tonight Paradigmers, as we wait patiently for some decent and hopefully exciting news just around the corner, lets now investigate just what this means.
Note: We have already covered Fast Track designation before:
https://hotcopper.com.au/threads/fast-track.4780603/
Definition of Breakthrough Designation:
The best place to grasp what this means is the FDA's website itself, let me quote it here for you:
"A breakthrough drug or therapy is intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development". 1
In 2012, The FDA set up this concept to assist with the expediting of the drug approval process after much public demand to speed up the critical drug approval process.
Whats Involved?
It appears the sponsoring company (thats us, PAR) must apply for this designation. The FDA has 60 days to get back to us and give us the go ahead or not.Fundamentally we need to show that our iPPS has a "substantial improvement" on at least one significant endpoint over current therapies. That's certainly the case in our situation but this is my humble opinion, we need the experts to concur alongside clinical trial data.
Whats the difference between Fast Track and Breakthrough?
Good question! While both of these designations have the purpose or intention of speeding up the development process for life threatening or serious conditions, the crux of the difference is breakthrough should "demonstrate substantial improvement on a clinically significant endpoint" whereas a Fast Track looks at clinical data which will "demonstrate the potential to address unmet medical needs for the serious condition". 2
Perhaps a subtle difference in designations but the result could be that we shorten the time to market, perhaps as much again as 6 months. In my mind I still conservatively estimate a good 2 years after the start but the Phase 3 Trial could easily be halted early if the results are outstanding and the FDA truly want to arrest the awful Opioid crisis and see this as being a real viable solution to curbing the horror stats prevalent in both AUS and USA and other markets.
All very good and fine Mozzarc but what are our chances? To answer that we need to first investigate a definition of Serious Condition.
What is a Serious Condition, is OA serious? Well ask any suffering patient! Look at the indirect consequences of current standard of care, any lay person would agree its serious, but we need something more concrete, lets go to a scientific, and more importantly FDA, definition of what a serious condition is and YOU make the call, do we make the cut?
Definition of a serious condition according to the FDA 2
I, and I hope you as well, have read the personal testimonies by the patients of the SAS program on here at Hot Copper, I personally feel they fall under this definition. This is a serious condition that hampers day to day life and yes, "left untreated" it will progress from a less sever condition to a more serious one.
Fellow Pardigmers, Importantly, Under Section VI (A) 3i 2, the FDA states clearly "FDA expects that such evidence generally would be derived from phase 1 or 2 trials. Nonclinical information could support the clinical evidence of drug activity."
Herein lies the cleverness of Paul and the team at PAR to gather as much real world evidence ("nonclincial information" from the definition above) from the SAS program to collaborate valuable information and evidence to support what the FDA will be looking for. Its just another Masterstroke along side the excellent patent work (BMEL specifically with OA) that has been accomplished and the Supplier Lock up. I cant wait to meet this guy, he, in my opinion, is a superstar no matter what the outcome is.
The other clue is to look at all the clinical trails most other drug companies have conducted in Australia, A SAS parallel review is rare. We, as 51 Cap have coined it, are getting the exam solutions before the test itself! Why the heck would PAR do this? Its because they are confident of the result AND in my view it adds to the mounting evidence required for the clinical trials. It was a risk worth taking, we'll find out in a few months time...maybe 6 months from now..maybe a year.
Benefits to us of this Breakthrough Designation.
Well the obvious one, speed we have covered....but some others in more detail:
1) Intensive Guidance on efficient drug development, it sounds like the FDA will work more closely with PAR during the process
2) Organisational commitment - this to me suggests added resources from the FDA side in terms of senior and experienced staff being designated and perhaps more of them being allocated to our case.
3) Rolling Review - from what I know, this means all the tasks don't have to be lined up in sequence, multiple fronts can be tackled at once saving time.
Furthermore, under Appendix 1 Section 5 (B) 1 2 the FDA states that if the sponsor doesn't necessarily apply for a Breakthrough designation, the FDA themselves can suggest that the sponsor apply for this designation if the FDA thinks it is plausible.
This is good news for us as we are covered if the FDA thinks we have a shot at this designation, the onus is not just on PAR, its a two way street.
How many drugs have had this designation, how many have been successful in achieving this status?
Check out the stats below for the last 8 years including 2019 so far:
Breakthrough designations in the past. Courtesy FDA.
Timelines, conservative/realistic -v- whats possible?
Ok this is a bit of a pie in the sky type question...just how long is a piece of string? My dad always said the answer to that is "Twice it's half length". There are so many factors and maybe unforeseen questions and hurdles...we don't know the timelines and pathways, we don't know if there will be many hurdles or back and forth questioning and answering between PAR and the FDA, but as a guide take a look at the below figure:
Median Timelines for the four possible designations 3
AA = Accelerated Approval
FT = Fast Track
PR = Priority Review
BT = Breakthrough
Perhaps around 230 days as an average? I would go conservative and round it up to maybe 250/270 days at least. A lot is at stake but this is also counterbalancedby the acute need and the empirical evidence we have already mustered in terms of the excellent SAS program, some 500 patients will surely add some weight to the clinical trials data.
Other Notes
All of the above is exciting enough, don't forget that if when we do get such a designation awarded to us, apart from me personally celebrating with a few beers, an expensive whisky chaser on the rocks and posting a few Congratulatory type High Fives in random spots on HC, the chance of a tie up/deal with a Big Phrama would also increase markedly.If you get some time, do check out some of the excellent references below, some great detailed reading which will add a whole heap of colour to my brief summary here.
Disclaimers
Yes the fun part. These are my opinions, you know its always best to do your own investigations and research. Timelines are highly speculative. PAR has fallen behind a number of times, its understandable as the team is not big, the scope of these projects are large and the emphasis must be on an excellent standard of work and attention to details and diligence, otherwise ifwe get a rejection, we will lose even more time and it could result in PAR having to do so much more work, endure costly delays and a hit to the SP as things get delayed.
Its in our interest that they take their time and formulate such important clinical trials in the right way to get the maximum chance of success.
On Monday next week we may see most shares fall (DOW fell 600 + points on Friday), even PAR may experience more rough times ahead, but to me at least, its an opportunity to look for some spare change and buy a couple more shares, whaddya think?
Be patient, dont risk more than you can afford to lose, but in my view it should make for some very interesting times ahead.
References Used
(1) https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/fact-sheet-breakthrough-therapies
This next reference is a 40 page doc but will certainly give you some more details about this possible pathway to commercialsation:
(2) https://www.fda.gov/media/86377/download
(3) http://www.pharmexec.com/how-fast-are-fda-fast-lanes
(20min delay)