Avacta Group, the developer of Affimer® biotherapeutics and reagents, has received approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) for its Clinical Trial Authorisation (CTA) in the UK for a phase I study of its lead pre|CISION™ pro-drug, AVA6000 pro-doxorubicin.
In AVA6000, doxorubicin has been modified with Avacta’s pre|CISION™ chemistry, which renders the modified drug inactive in the circulation until it enters the tumour micro-environment. Here it is activated by an enzyme called FAP (fibroblast activation protein), which is in high abundance in most solid tumours but not in healthy tissue such as the heart.
In animal models AVA6000 has been shown to significantly increase the amount of active drug in a tumour compared with the heart and has significant potential to improve tolerability and achieve better clinical outcomes for patients.
The MHRA CTA approval is for a phase I clinical study and is a first-in-human, open-label, multi-centre study to be carried out in the UK in patients with locally advanced or metastatic solid tumours, which are known to be FAP positive including pancreatic, colorectal, breast, ovarian, bladder and non-small cell lung cancers, squamous cell carcinoma of the head and neck and soft-tissue sarcoma.
The timing of dosing the first patient in the study may be affected by the ongoing COVID-19 pandemic and its effect on hospital resources. However, it is anticipated that the study will start around mid-year.
Alastair Smith, Chief Executive Officer of Avacta Group, said: “I am delighted to receive this approval for the AVA6000 Pro-doxorubicin phase I study from the MHRA. This is a significant milestone for Avacta and opens the path to a potentially transformational clinical proof-of-concept study for AVA6000 and the pre|CISION platform.
“If the AVA6000 study shows that the pre|CISION chemistry is effective in reducing systemic toxicity of doxorubicin in humans, then it can be applied to a range of other established chemotherapies to improve their safety and efficacy.
“This would open up a pipeline of next generation chemotherapies for the Group with significant clinical and commercial value in a chemotherapy market that is expected to grow to $56 billion by 2024.
“I look forward to updating the market on the timing of the dosing of the first patient and on the clinical data in due course.”
Professor Chris Twelves, AVA6000 Study Chief Investigator, Leeds Teaching Hospitals Trust and the University of Leeds, said: “This is tremendous news. When I see patients with cancer, I want to offer them more effective treatments with fewer side effects. My team are excited to be part of the AVA6000 Phase I first into human study and we look forward to enrolling patients into the clinical trial.”
Neil Bell, Chief Development Officer of Avacta Group, said: “The AVA6000 clincial trial authorisation approval represents another important milestone for the pre|CISION platform and AVA6000 programme.
“Working in partnership with the UK regulatory authority, the Medicines and Healthcare products Regulatory Agency (MHRA), Avacta has obtained approval to initate our first Phase I open-label clinical study to evaluate AVA6000, a novel FAP-activated doxorubicin prodrug.
“By utilizing FAP activation as a selective drug delivery system the pre|CISION platform provides the capability to deliver chemotherapies to the tumour microenvironment whilst limiting severe and life-threatening toxicities in non-target tissues. pre|CISION has the potential to change future treatment paradigms for many chemotherapies which have not yet optimised their clinical utility.
“The next key milestone for the AVA6000 programme is to dose our first patient, planned for mid-year 2021 in the UK. Notwithstanding Covid-19 restrictions, the team are energetically working towards achieving this milestone, which will see Avacta transform into a clinical stage company.”