research reports and media, page-3316

Hiya dogman,

I think I need a pro forma for this question, (Hrdwrk asked it not long ago).

I've included my answer at the bottom of this post.

The long and the short of it, hard to impossible to come up with a date, there is a lot involved...there are a number of things that need to be addressed. It could be as early as Q1 next year, it might be as late as end of next year? Depends really on the flow of data, quality of data, how the evidence pans out. Yes DMOAD aspects will greatly assist such an application but there is a lot involved. Conclusive DMOAD isnt necessarily a pre cursor to the application in itself. Its a strong surrogate biomarker(s) that will be key. Get these from multiple sub groupings (Bipoeds/structural) and you have an increased chance - in my view only.


I also briefly posted about this last night which you might not have read yet, here is a paragraph:

-----
ACCELERATION

I have a number of posts scattered through HC over time regarding my thoughts on AA. I'm wary of getting too carried away too quickly. My own research does show a very clear pathway to the holy grail of AA. There are fairly clear indicators of what is required and indeed what we are capable of.

A number of ducks are required to line up would include , but not perhaps limited to:

6 Month data - 008 and great progression of our surrogate biomarkers (yeah that was plural)

Top Line 002

DSMB reports with excellent safety observations intact

Min effective dosing determination

Consistent data release from here on in



Get those 5 ducks above aligned....you have a serious case.


Now add in a Mozz special of not one, but several surrogate biomarkers, and to further boost our case, turbo charge it...add biomarkers from MULTIPLE BIPED groups...add a little structural data and you have a winning formula...so winning that there hasn't ever been a drug like this in this realm of immunology and inflammation leave aside safety profile, durability of effect, effective reduction of pain and increase of function. Our time is coming (spec statement, though perhaps getting less spec these days and in future days?).

Yes I believe PAR would be seriously putting work together to form a case of AA once and if we have all those ducks lined up neatly...





The thing I like is that I sit here today and imagine, just imagine that STILL not many know about us! Isn't that fascinating. I believe PAR has learnt a stack from prior trials and results....not just what Torpy indicated in his post. I'm talking about HOW to release data, WHEN to release data and in what format.
---------




---- Posted 2/08/22 -----
Hi Hrdwk,

Lets take a sneak peak at this...of course remember to not rely on just me, its mainly my thoughts, I could be mistaken:


WHAT IS AN ACCELERATE APPROVAL?

Quite simply, for an accelerated approval (AA) the drug under investigation must meet a number of criteria.

Firstly, it must address an unmet medical need in some sort of serious condition.

OA now meets this criteria. Nah its not just me saying it...the FDA recognises that it falls under this banner,
We are already in a better place by being awarded a Fast Track designation, this can be a bit of a precursor to an AA but not always.

But a sponsor (that's us) doesn't want to put in an application prematurely.




_{Don't jump the gun, it will end in tears.}
.

You want to have an adequate data set and you want to get the timing just right.When I say adequate data set I mean volume but I also mean consistency and a concise-as-possible range of results. Too scattered wont be as convincing as a narrower data range.It has to be somewhat statistically meaningful?


Ask the questions, how can we prove our case, what does the FDA want?



WHAT DO THEY LOOK FOR?

Positive therapeutic benefit is a term they look at. They are wanting this clinical benefit as a result of an observation of a surrogate biomarker.

What does that mean? It means some sort of observation that is an intermediate endpoint. For cancer, it could be a reduction or shrinkage of a tumour.

In the case of the tumour as an example, "... the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer". ¹

...and this shows us the exact light, the exact goal that the FDA are trying to achieve. We see them sometimes as the high and pompous judge...the ultimate umpire. But what we forget sometimes is that while they are trying to keep patients safe, they are also wanting to get good drugs out there in a timely manner while still being rigorous and keeping the population safe.



_{FDA? Don't fight the Fed....FDA.}


Its pains me that they took so long to get us over the line in terms of IND..,.but I kinda justified this a bit by saying that one day, if all goes to plan, we could actually be selling our drug not just to a few lucky athletes not just to a few rare disease MPS folk...but to the wider GLOBAL population.

Guys, selling a drug onto a niche market subset is one thing, being allowed to sell it to literally MILLIONS of people is quite another. We will eventually wipe out the scourge of opioids....we may address not just OA and Pre OA....I'm talking all sorts of pain conditions at one heck of a scale...(my views)...they are going to want to be somewhat sure that what we have is quite safe, let alone effective and efficacious.


But lets get back to us...What is an example, like the above tumour example, for us? Well I'm talking bio markers that depict what's happening not just in the serum, but also the synovium. The synovium is a hot spot, we know its an integral part of OA and its manifestations, we know the fold increases that it can elicit...we know it is a pre cursor to a very much increased chance of damage and later, joint failure. No wonder this 008 study is so important., so potentially pivotal.

I don't know currently how many ordinary (non HC holders) know about 008's ramifications, but we know.

Other than bio chemical biomarkers, we are also looking at the very important structural biomarkers...

The spirit of an AA is to attempt to get a good drug out into the community and not have to wait all the time it takes to show some of these more longitudinal endpoints. Yes we still have to show the FDA our final results but why not attempt to reduce suffering by getting such vital drugs out there. Its for this reason we see most of the AA drug applicants being in the oncology space. However, as the FDA have clearly defined, we also meet this criteria. Whether it be direct or indirect, having OA and moving up through the KL grades do lead to many other health issues and thus the classification of serious and unmet need.



BUT DONT FOR A MNUTE THINK THIS IS EASY STREET


_{No...its easy street AFTER a lot of effort, a lot of thought...a lot of late nights, a lot of meetings...Thank you Par. and staff.}


What I mean here is that the FDA will apply the same rigorous standards to an AA as well as the traditional pathway:

The FDA uses the same basic standards for approving drugs via the Accelerated Approval Program and the traditional pathway. Accelerated approval drugs are assessed against the statutory “substantial evidence of safety” standard to determine if sufficient information demonstrates “a drug is safe for use under conditions prescribed, recommended or suggested in the proposed labelling.” ²


WHEN?

So to answer your question HRDWK, I have no doubt that a good result from 008 will be another hurdle we have crossed on a pathway to a quicker result such as an AA. BUT I'm also mindful that we still need to show a number of things first.We still need to get through Part 1 of 002. We still need to build up our data from a chosen dose of 002. We still need to show consistency of data at some sort of scale. We still need to build all this into a well thought out dossier and link the findings of 008 with 002.

So when could we reasonably expect the possibility of consideration for filing an AA?

Well it depends on a number of factors, prob the most important is the data.

If the data is good...

.....if the data is consistent.....

..........then we can start to think about this AA possibility.


Yeah It's a Mozz post, yeah I know we all want the exact date, nah that isn't going to happen, but how about a small clue?Lets cross over the FDA's own web site:








That's the clue...the red circle above....




DISCALIMERS

Now I'm not saying its a definite, I'm not saying we could/would file before or after...I am saying that the chance of maybe filing COULD possibly be somewhere around the tail end of 002 and perhaps just before or just after 003 kicks off. Don't forget, we need to pass through some hoops first before it even begins to be a consideration. We need our data to be strong, consistent and meet those endpoints and observations...



Completely my opinions here..


Lets see how this all unfolds yeah?




- Mozz







REFERENCES

1] https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval
2] https://avalere.com/insights/understanding-the-history-and-use-of-the-accelerated-approval-pathway#:~:text=Accelerated%20approval%20drugs%20are%20assessed,meet%20the%20FDA's%20standard%20for







ps: Isn't it just so much better when there is Green on your screen?
I'm really loving the parcels I managed to pick up in the last few weeks...I'm locking those away in the drawer without the key...