In 1982, my mother (who never smoked) tragically died of breast cancer at the age of 39. She was given one of the world’s strongest chemo-therapy drugs, doxorubicin, which worked for a couple of years. But unfortunately, after 6 or so cycles, the treatment had to be stopped due to toxicity, and the cancer later spread.
Fast forward 40 years, and this may be about to change.
Today, after receiving approval from the Medicines and Healthcare products Regulatory Agency, Avacta (AVCT) announced that the first patient in cohort 5 of its Phase 1a clinical trial had been dosed with 250mg/m2 of AVA6000, or Prodoxorubicin.
This is excellent news for numerous reasons.
Firstly it confirms once again that the safety profile of AVA6000 is considerably better than conventional doxorubicin. If approved, its lower toxicity should also allow patients to be treated for more cycles than is currently the case, and perhaps even at a higher potencies too. And we already know from biopsy and urine data that the 'chemo-warhead' is being successfully absorbed by the tumour, meaning improved efficacy.
To put this into context, the maximum approved dose for doxorubicin as a monotherapy is typically 60-75mg/m2. Avacta's dosing regime has already been increased from 80mg/m2 in cohort 1 to 120mg/m2, 160mg/m2, 200mg/m2 and now 250mg/m2 without any material concerns.
So what comes next?
Well, one of the key objectives of the Phase 1a trial is to identify the maximum tolerated dose which can then be used within Phase 1b and beyond. According to Cancer Research UK, doxorubicin slows or stops the growth of cancer cells, suggesting that the length of patient treatment and number of cycles may be just as important as the potency of the drug.
CEO Alastair Smith commented: “We are very much encouraged by the positive safety & tolerability data emerging from the dose escalation phase 1a study of AVA6000. The release of active chemotherapy in the tumour tissue & the safety data being generated are also providing detailed insights into the preCISION platform, which add significant value to the technology and confirm its potential.”
Doxorubicin is still considered by many doctors to be the gold standard’for treating several hard tumours with a total addressable market of approximately $1.38bn, highlighting the commercial opportunity Avacta is targeting - and Prodoxurubicin also has the potential be used in combination with new treatment regimes such as Checkpoint inhibitors and CAR-T therapies.
And if things go to plan, it's understood that regulators might even offer AVA6000 an accelerated Phase 3 clinical trial, which would shorten R&D timescales and cost.