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Thanks JT - she seems a very straight and balanced person . My take on that is there are further benefits over standard dox with that approach. For example we see greater tumour shrinkage or the drug is even better tolerated. (Mouse photos). My understanding is dox stops tumour growth whilst its given but when it has to be stopped then brake comes off. Therefore treating for longer would be better if there is no additional benefit. Hence they are thinking ava6000 is even better than first thought.
However, im dubious about 12 months but fantastic if im wrong. Right pass me what car magazine again.
I meant to say that i think more frequent dosing within 18 weeks will be about greater efficacy thsn standard dix. See mouse photos
My belief is that the benchmark is to dox prevents the disease progressing and it does this within the standard dose and three week interval.
If ava6000 is aiming to show equivilence to this then it may be that more frequent dosing is necessary e.g.18 x weekly cycles. The implication tbough was that ava6000 could be given for longer hence keeping the tumour in check. Dox stops at 18 weeks whereas ava6000 continues for 54. This route would mesn it is 18-24months to get final PFS stats.
Both of the above are possible within same study - two arms. Im thinking more and more that avacta will build an interim analysis in which could then match AS timeline especially if recruitment is quick.
In terms of pharma deals it is standard to pay upfront for options to continue. Lots of deals have stopped when milestones not hit or the buyer has a change in priority. Option to stop with buyer. The deal with LG looks like this x sevetal compounds. So talk of cash in bank ignores future milestone payments from LG - ind approval will almist certainly be one.
The size of the payments are proportional to risk. Hence keep in house for now aoproach. My guess is son of velcade will go cheaper than we want this year but will have higher thsn 15 % of sales attached. Such a move would highlight precisiin to others - i expect a couple of deals to be announced q3 next year (after P1a).
Thanks for this. Great stuff.
Was good to see share holders being able to ask questions live yesterday.
I wasnt sure about some of the answers. One discussion revolved around P1b and the timelines. My calcs are that if it goes to 18 cycles then this is 54 weeks. Im thinking just the treatment phase for each patient is over a year. Have to top and tail that with patient recruitment and data analysis.
Options are for interim analysis but given primary efficacy variable is progression free survival and normal dox achieves this whilst its been given the timeline still looks optimistic. At the time point where one group has received ava6000 for 18 cycles and the other has had dox for 6 + 12off cycles would presumably show a bigger difference.
If ava6000 goes beyond dox and actually reverses the tumour then interim could yield a result. I am concious of the photos of mice tumours and reports of ava6000 providing benefits to some patients with tunours not normaly treated with dox.
The talks were very confident yesterday and gave a sense that current data is very good. Just not sure about timeline - i could have it wrong but several have been missed before and that just enables the knockers to jump in.
Dont touch the Shorts bread
Rich T
I suspect they have continued beyond 450mg on a compasionate use basis. The slides were presented at SD when the most any patient had received was 8 cycles. Two possibilities
1. Patient had received more than 8 cycles but 9 and beyond not included in trial dataset. This matches the data from comparison has well
2. Patient has had dose changed from every three weeks. Maybe they monitor with bloods and hit tumour when feel its required
So one patient has had at least 8 cycles after over a year of the trial running. The median was 2 cycles. Hence im a little bit dubious of the 24 cycles calculation. I find Occams razor handy.
Following my own advice im pleased for those human beings who have benefited and sad for those that didnt. As we move to higher doses maybe all patients treated will see some benefit. Lets hope so
The biggest problem with the 24 cycles of treatment is that avacta recently published information in their AE table - the one they boot strapped to data from the Announce study.
In this table they say the range of doses is 1 to 8 with the median being 2. I dont have a calculator but C1 dox nieive patients may be within the stated cummulative dose maximum stated in the trial protocol after 8 cycles
The table also shows a much improved tolerability against dox it isnt side effect free. By pausing treatment for 3 weeks the incidence and severity remains low.
Some (if not all) patients are responding to a treatment that is not normally used for their condition. That is amazing and offers a hope that Avacta will bring a new, effective and well tolerated therapy to even more patients. This will take time but once that hard evidence exists then as a wise man once said - ava6000 becomes the new standard over night
So current protocol is dose every three weeks. Im trying to work out the term "no dosing holiday" could mean.
Is this no holiday equivilent to a dose of ava6000 every week? Or every day. Or twice a day. Or a large loading dose with hourly top ups. Or a continual infusion delivered from a canister like a scuba outfit.
If there is no dosing holiday then rationale for the chosen posology will be part of the patient informed consent pack. No doubt will be huge part of the discission over pork pies and tea at the interval and im expecting follow up flyers, posters and a shumper wearing video conference at the very least.
From the trial protocol....
"Drug: AVA6000
AVA6000 is a FAP-activated prodrug of doxorubicin. AVA6000 will be administered via IV infusion every 3 weeks. Dosing will occur based on the calculated patient's BSA on the day of dosing"
Imagine if a patient presents an individual patient image data at AGM
I think trial includes imagery (FAP-PETI) but some form of monitoring would be standard practice. At some point.....
Lol.
Imagine if AS presents an individual patient image data at AGM.
People in the trial are volunteers. They enter the trial with the balance being benefit to others rather than themselves.
If the trial therapy appears to benefit them then everyone here should forget the point scoring, the playground insults and the football my team is the best attitude and chill. It's just fr/cken brilliant. Grab the poms poms and celebrate for that human.
From an investigator point of view if x dose appeared to benefit the patient then yes continue at that dose especially if there is no data available at higher doses - after all its still an experimental therapy - softly softly. However, if data emerges that a higher dose is likely to benefit thus volunteer to a greater extent then you would have to be some sort of demented idiot to suggest this volunteer should be denied thus opportunity because they might soil your data.
Apologies I'm really p\zzed.
Ex-china?
I like the fantasy calculator. It saves me p/zzing I'm my pants when I want warm feelings
Full Metal Jacket?
I've borrowed the fantasy calculator and am rounding 49 up to 5000. If a post it enough times I convince myself it's a fact.
In response to PL and at the risk of watching shadows on the wall.
The decision to continue treatment beyond the trial schedule would be on an individual patient basis and the response seen in that patient. My guess would be
1. Only patients seen to have a response (e.g. no disease progression) would be continued.
2. Patients not seen to respond wouldn't be put on treatment at a later date as Cohort doses increase
3. The dose given would initially match the dose they responded too - wouldn't be higher since that negates the 3+3 rationale and carries commercial risk (eg higher dose given and SAE experienced)
4. Has evidence of tolerability at higher doses emerges the clinician could consider and apply to have the compassionate use dosage increased if there were reasonable grounds to believe benefit outweighs risk.
All guess work but I think the reasonable man approach works well in these scenarios. What you cannot do is go at it like a pig at a tatter on the basis that if a little is OK then bucket loads must be great.