Not that easy. Yes PAR can definitely start to tee up ideas and convos about funding and the requirements beforehand but the actual funding I doubt they will execute on this at least until after the FDA have sanctioned the Stage 2 P3 and ensuing Confirmatory.
It's good to sometimes go back on the previously stated material, here is an excerpt from the AGM last year that gives more colour on just a sample of what's involved.
--------------------------------- Extract from 2023 AGM ----------------
Question:
In light of the last two announcements of Duration and the Structural (cartilage volume for example) world first data that we got. (6 bio markers mentioned plus the observations of 40 micro meters depletion in PBO -v- 60 positive, active iPPS), is there any scope for a reduction of numbers particularly in our 003 which stems back to our statistical significance, is there scope to reduce these numbers and who takes charge of this (Biostatician/sponsor/authority?)
Donna - It takes a village.Some of the people that are involved include Medical and clinical development teams, obviously statisticians are involved.
"Of course we were very impressed with the effect size which we saw in 008."
Keeping in mind in this small study,we have taken the effect size in this study and compared it with other drug effect sizes and we made a determination of what do we need to be competitive and be competitive and win.
We set the bar at a reasonable level, where effect size we choose is clinically important, and competitive. We get those answers by working with the clinical team and the statistician.
At the very core of our statistical support is a statistician known as Jim Bolognese who has worked almost this entire career in OA and other musculoskeletal indications He knows the end points very well, he understand the type of variability you may see with certain endpoints and he knows about the challenges of placebo in pain studies.
Based on what we saw in 005 and 008 we did a weighted joint effect size and compared this to what drugs are in the market. There are of course other unique attributes of PPS such as the duration of the effect and the combination of the clinical results with liquid biomarkers and structural effects that we have not seen with any other competitor.
We want to pick a bar that is clinically relevant but we want to win in terms of showing statistical significant results in the pivotal study.
" If you put that together with our structural effects and our biomarkers - It puts us in an unique position ".
It is possible that the number of subjects will reduce slightly. I say slightly because the actual number calculated may be much smaller but we adjust it for dropouts.
Numbers must include regional and heritage profiles.
It does take a village to come up with the right number of subjects and right patient population to have a successful program.
"We think that 008 has been very very informative in terms of not only the pain and function responses but now understanding that that twice weekly dose is also heralding a structural effect at a time when most people would say that it is premature to expect to see anything from an MRI".
--------------------
The key point above that I wanted to highlight is the statement about reduced numbers. I believe there is a chance that numbers can reduce, perhaps not by a lot but every patient less will be a material amount less we need in terms of spend.
The 008 is extremely important here as we achieved statistical significance not only in 008 but we got it right throughout 005 as well. This data should be considered in formulating the second stage. If it takes a bit longer to do this, so be it. It is in our medium to longer term benefit to do this, it will save millions and result in a quicker read out.
We all want that.
"Slow Is Smooth and Smooth Is Fast"
Sometimes we need to take our time in order for the entire program to go quicker.
Single Left click to enlarge. Ref: https://www.cristcot.com/advisory-teams
(20min delay)
