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Looking at the P1aA2 design, Avacta wants this to maximise data prior to P2. Think of it as a brand new drug. If a small study shows safety and suggests improved efficacy, then this is the trial to replicate in the big P2 trial.
If their evidence to date suggests fortnightly dosing will markedly improve efficacy AND massively reduce toxicity, it will get prescribed to more patients than plain doxorubicin is at present. Both as a first treatment and a proposed maintenance therapy. This is huge, and well financially massive. Itās honestly worth the wait. This is more than icing on the cake.
May I suggest this: Avacta has lab based research showing a marked improvement in efficacy with a fortnightly dosing regime? Or their data analysis thus far indicates improved cell death with a fortnightly dosage regime.
P2 will be the licensing trial for AVA6000. Itās honestly best they get this one, the first one, right. Getting approval for a three weekly regimen, then seeking PL alteration for fortnightly dosing will take another expensive, in time and money, trial. Honestly best to get the first P2 to be definitive trial.
Playing Devilās Advocate, maybe the FDA or āinterested partiesā suggested the two week trial? Obviously we donāt know all of P1a data, but Iād be surprised if it was enough to go straight to market. A hybrid P2&3, for a designated orphan drug, would make sense. I honestly donāt think theyād be doing the P1aA2 without very good reason. Because of exactly what we all want, P2/3 to get approval and start enrolling.
GLA
Ice, Iām going to respectfully disagree about the two week trial. My reason: plain doxorubicin has had to be given every three weeks because of its side effect profile. The present P1a for AVA6000 has proven its safety in a like for like dosing timescale. But itās a distinct possibility doxorubicin is more effective if given more frequently. Unfortunately this needs its own P1a safety data to be taken forward. Depending on the P1aA2 (fortnightly) results, the P2 trial for AVA6000 may well be a fortnightly trial. Thatās potentially world changing.
GLA.
Let me clarify:
Reading the posts today has been more depressing than normal. The lack of understanding about the route to market for AVA6000 vs a brand new molecule staggers me. The failure of people to research the Orphan Drugs get trialed. Yes this takes funding, but I honestly think AVA6000 is closer to market than people realise. A combined phase 2&3 trial for STS is relatively quick. The funding can come from a variety of options.
I respect a cautious approach to investing, but a well researched one as well.
GLA.
Couldnāt agree more. Looking at peopleās lack of understanding about Pharmacology and Pharmaceuticals makes me feel so sorry for them. In the meantime something is happening in the background. Possibly a placing. Drugs cost money to develop and trial. The only question is how much, and which options will Avacta have to make it happen?
GLA
CLINICAL TRIAL DESIGN FOR ORPHAN DRUGS / RARE DISEASES:
Worth a read. AVA6000 can have a more bespoke trial to get it to market.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613711/
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Ensure confidentiality??!
A useful retrospective analysis of the use of plain doxorubicin against Soft Tissue Sarcoma. Interesting to see the continued use of doxorubicin suggested as a maintenance therapy. At least there is a robust dataset to compare AVA6000 against.
https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/s13569-020-00137-5
The 10 points seemed very reasonable to me.
Answering the point about fortnightly dosing,
Agree limited data released so far. Iād like to see the data for each case. Doxorubicin levels in the tumour cells and its FAP status is essential to know.
Fortnightly dosing: my take is the evidence so far suggests this is safe and will improve efficacy. AVA6000 should allow a higher peak and sustained higher intratumour levels of free doxorubicin. Growing evidence itās not just DNA replication damage that causes tumour cell death. Fingers crossed we see enhanced killing with higher drug levels.
Not sure if a higher dose - peak and total delivered to the tumour - might help reduce Multi Drug Resistance.