Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
Leek
Yep - changing posology would result in a different shaped ava6000 exposure curve - longer but flatter. Is the killing of tumour cells max concentration dependent or more about exposure (auc) type stuff. To be honest pharm101 was on a Friday afternoon at which point I was already p1ssed.
P1a continues though with same dosing approach - suggests safety committee are happy new data is still time be had.
Is mtd for normal dox at same systemic concentrations as dox appearing in systemic with ava6000 ? If so then disease hitting tumour would be massive. I'm thinking they haven't adopted that approach and tolerability being much better is their aim
Not long now in real terms. Im thinking private plate for the what will be newly released 2025 mx5 electric, 4wd roadster
Think you have to consider that ava6000 converts within the SMALL volume of the tumour. I don't believe 100% gets converted but to achieve high concentrations it doesn't need to.
If conversion is limited to tumour then presumably any dox seen systemically is related to leakage from a SMALL volume to a much LARGER volume. This results in dilution to a much lower concentration.
If 100% of the 3x normal dose was converted and leaked out then systemic conc would be correspondingly higher than normal but tumour concentration would be through the roof. Hence the pk of Ava6000 is complicated and will not be released on an ongoing basis until picture is clear. This will be at end of trial not halfway through.
I have mentioned fap saturation before - the fact that they continue to increase dose suggests it hasn't be hit yet but if it occurs at C6 or C7 then MTD bench marked against normal dox may never be hit.
RAH has submitted a question about why they didn't answer the last lot of questions. The calculator needs feeding
there is never a magic calculator when you need one.
if the chances of rns tomorrow is 50% on that rationale the chances of an rns the following day is also 50%.
so the chances of an rns tomorrow or the day after is 50% + 50% (using similar approach to stats).
this means the chances of an rns this week is 100%.
i'll laugh my ***5 offb if this prediction comes true but time be fairbi heard september mentioned on my last trip to mcds.
this message will now self destruct and reappear on tw4tter
We really should revisit this on April Fools day.
The number of possibilities is not the probability of one of those possibilities occurring. Otherwise I'm doing the lottery on Friday with a 50% chance of winning.
Was hoping someone was going to mention Monty Hall
My amateur view is if ava6000 is able to disrupt Stroma then it will make all other therapies more effective since they can get in to to the site of action
She was busy working her way through all the questions submitted last time but not answered.
Now trying to work out how to use excel to calculate RoI on new purchases
The inclusion of a SoC arm and primary efficacy variable screams P2
To me at least.
The reformulation nature of ava6000 rather then NCE suggests shorter pathway to regulation. That's suggests not definite (apologies I the fantasy magic calculator on blink).
I suspect increase in numbers but with an interim analysis built in - moves from 1b to P2/3 - far more pk and safety data including biopsies than original P1a planned. OK fantasy calculator checked and working
How I long for a leek....
Add my tuppence worth. I like the thought ava6000 is a pro drug. P1a is about the pk not efficacy. Phase III is efficacy but as Rory has suggested we already know the efficacy of dox.
There must a regulatory route that negotiates the spectrum between generic, modified generic, prodrugs and NCEs.
Big P are probably more adept at this than Avacta.
My thoughts are we progress to P2 rather than P1b (not even sure what that is) and build a case for approval on basis of efficacy of dox is known. I'm an optimist
BP sees this opportunity and offers £200 ex-China shortly after full P1a data published
To be honest I haven't seen any posts that claim once cleaved from ava6000 dox is anything but dox. There are lots of posts decrying FUD of this nature but no actual posts. Apologies if I've missed them.
Where do you sign up for the next trial. Just asking. For a friend..
I take a slightly different view in that there is two types of analysts working in IIs. There are those that run the financial numbers and then there are the specific area specialists. There will be more than one oncology expert working in financial houses, jet setting to lots of lovely places and advisory boards are fairly easy things to put together. These people probably have a different and possibly better informed view of all the opportunities than most PIs. The caveats they place when telling the numbers guys is that the data is not yet availsble - equates to risk in a high risk area. No one loses their job by advising wait until data there even if it means entry is higher.
The good news is that this could mean large sums sitting on the side line waiting for definitive news.
I continue to hold with top up on stand by
The forecast of 4 cycles to find MDT must have been based on animal data.
MDT is correlated with systemic dox
The need to extend the number of cycles may be because systemic dox is lower. Several mechanisms for that - some good, some bad.
I wonder what the dox levels were in animal models in tumours. We have release of dox from ava6000 and increased doses should increase tme levels (otherwise stop now).
My take. Ava6000 behaves differently in humans than mice. Trial continues until max dox in tumour vs systemic exposure is identified. Not there after 4 cycles but 7 will be enough given that f/c based on human data
Let's say ava6000 is going to be used to ensure pfs to match the use of normal dox.
We can be conservative and say every month rather 3 weeks so 12 cycles per year. This doubles pfs.
At $10,000 per cycle (a AS discount). That's $120k per patient per year.
US 13,000 patients
That's $1.5B. For one indication, in one country.
Needs a QALY approach to pricing rather than £/mg compared to dox
Olaratumab is supplied as a sterile, preservative-free, clear to slightly opalescent, and colorless to slightly yellow solution.9 It is available in 19-mL and 50-mL vials containing 10 mg/1 mL with average wholesale prices of $1,098 and $2,889, respectively.
The FDA-approved dosing for STS patients is 15 mg/kg of IV olaratumab on days 1 and 8 every three weeks,
A70kg person would need 70x15= 1050mg
So 2large x $2889 (+ a bit) twice per cycle. So minimum about $12000 per cycle.
Now compare ava6000 with Ola - even the promise before withdrawal.
If ava6000 can deliver what ola promised then its $12,000 per cycle. Why would you price it any lower except in China
Not sure the pricing will be modelled on like for like per mg of normal dox. Pharma companies don't work like that and neither do regulators. This will not be sold as an improved generic - it might replace dox but that is true of other non dox based drugs.
In effect the price will be based how much is an extra year of quality life worth. The benchmark is all the other drugs out there especially oncology.
Then there is the treatable population expansion argument which multiplies this. So yes, ava6000 sales value once commercialised will be many times that of generic dox. It will replace dox overnight apparently meaning product cycle is longer than normal - however need to get a move on
We might get answers to the questions submitted at the agm. I submitted a couple including cod or haddock