Hi Ceviche,
Ok let's take a closer look. Here is what Mixed Bag said:
They appearto have changed the specifics of the trial fairly significantly. They are now appearing to be looking at pain reduction, function improvement and DMOAD in the P3 trial. Patient monitoring to 405d and decrease in patient numbers are very significantly different to previously announced.So I'm curious as to whether these changes have already been negotiated with the FDA or whether PAR have submitted all these trial changes in hope and the FDA are going to chop it around significantly. I would hope that it is not the latter, because it would be very irresponsible to be publishing these changes if they are completely unrealistic or haven't been negotiated with the FDA.Here was my original response:
MixedBag -
Yes also agree with your comments. Also, at least from a statistical point of view; that n has dropped due to SS achieved in 005 and 008. It's new data but it's also a stat. plan based on concrete data. It is up to the Sponsor together with the Bio Statistician to formulate that plan and submit it to FDA. The onus is on the sponsor, if they get it wrong it's the sponsor that will pay the consequences.------
Ceviche, you ask whether I think PAR are changing course.
The absolute answer I would give is..... YES!
You also ask why.
That's a question that needs a much longer answer, in truth it would actually take me hours to answer properly. But let's try a more concise answer.
PAR know how long things take. Haha - We here at HC have been voicing that over the years...C'mon PAR...why are you taking so long. Why are you saying it will be done here and it's there...why are you always late?
So PAR know that to do a couple of Phase 3 studies in tandem is gonna take a long, long time. No one, even some of the staunchest LT'ers don't have a stomach for that. PAR are very very conscious of the fastest pathway to market now. But PAR are also realistic and know how long these agencies and procedures can and do take.
BUT......and it's a big but...
They also managed, at the same time, to acquire such amazing incredible data that NO ONE EXPECTED, that wasn't really supposed to happen.
I really , honestly know that to be the truth. The 008 study was NOT at all powered to show what it did. You are simply not supposed to get such SS (known as Statistical significance) when your n is less than 20. Unheard of. Then add that same fact to the idea that this is a pain trial and it's double blinded against placebo. My point is that placebo and pain are a potent mix and you are automatically having to beat some very large hurdles.
How was that possible? How did we get SS on a number of key measures with such a small n?
How did that happen?
There is only
ONE reason it did, that it could ever achieve SS on such few numbers - and that was
Drug Effect Size.
Mixed Bag mentions not only DMOAD but the 405d. Indeed our original submitted protocol (known as 002 stage 2) only had a reading at Day 168.
However, in light of the glorious 6 month and 12 month data observed in 008, this was PAR's chance to add a little time BUT include one very, very important reading, and that was the 12 month follow up.
The SS that we achieved in 008 with only sub 20 patients gives us an incredible opportunity:
It's to give back to the shareholders that are upset because we are taking longer and costing more.
What do I mean?
It's reduction of n. No longer are we talking some 470 patients plus in Stage 2...it's down to just 390.
It may not seem like a big drop, but it is. A 17% drop in numbers will translate into less costs AND less time to recruit and enrol. It all helps.
But more than tangible expense and time, it's also validation that the 008 stats were so good, hinged to the drug effect size.
This is gold.
Remember, it's not just you and me getting this good news...it's the potential partners, the future funds that may join us. This is the proof we will give them that our evidence is so good that our P3 numbers are LESS!!!! I can't tell you scientifically how good that it. It's a sure proof of our raw data being so good and so valuable. This translation will come. It's my view but it will be a fact. The stats don't lie.
Ceviche, you tell me., What is the average patient population in an FDA sanctioned P3?
Specially one that involves a pain indication? Its usually in the multiple hundreds if not thousands.
We normally have a comparator arm. There is no competition. There is NOTHING that's SubQ for OA with our safety profile and broad MOA.
We are it.
My guess in terms of Mixed Bag's great comments and thinking is that I suspect that PAR have worked very closely with their experts, KOLS, statisticians, Reg teams and Clinical etc and have come up with this viable new plan. Don't forget, the onus is more on the sponsor to get it right. The FDA really just casts their eye over from every one of their department's views and approves/disapproves/suggests modifications on it. If PAR didn't include the additional 12 m read out it wouldn't phase the FDA, it's no skin off their back. But it will mean the world to us.
You show durability at 12 month (let alone 6 month let alone 56 days), you got a whole new ball game in play.
The party that partners up with us will understand what that is worth.
Hope that helps.
DYOR etc
PS: A dilutive CR? I very much doubt it, but that's only my opinion, I've been wrong in the past!!!
If we have 20 mil in the bank and our burn is circa $6, that's 3 quarters, by then we will have something in place.
Ref:
https://clinicaltrials.gov/study/NCT04809376
(20min delay)