Kazia Therapeutics advances human trials for lead cancer drugs during December quarter

Oncology-focused and clinical stage biotechnology company Kazia Therapeutics (ASX: KZA) has reported strong progress on the development of its lead drug candidates during the three months to 31 December.

Work focused on studies for brain cancer therapy paxalisib, particularly the international GBM AGILE study into glioblastoma driven by the Global Coalition for Adaptive Research.

The study already has several dozen sites running in the United States and opened to Canadian hospitals in November, with the first site being Sunnybrook Health Sciences Centre in Ontario.

Additional sites are in the process of rolling out.

New drug approval

In December, Kazia and China-based Simcere Pharmaceutical received notice that an investigational new drug application for paxalisib in China had received regulatory approval.

The approval is a critical step in launching GBM AGILE in China, and in potentially pursuing other clinical trials of paxalisib.

The study is expected to open to recruitment in China by mid-year.

Adaptive design

The GBM AGILE study initially focused on the US, where more than 40 leading cancer hospitals are now participating.

It uses a sophisticated and novel approach called ‘adaptive design’ to readjust its statistical power as it goes. This approach has the potential to greatly accelerate timelines and reduce costs.

If an answer becomes clear after fewer than 200 patients, the study will conclude early, and Kazia will use the final data to submit a new drug application to the US Food and Drug Administration (FDA).

Phase two paxalisib study

In December, Kazia announced positive top-line final data from its own phase two study of paxalisib in patients with newly-diagnosed glioblastoma.

The study reported a median overall survival rate of 15.7 months in those treated with paxalisib, compared to 12.7 months with existing standard of care drug, temozolomide.

The median progression-free survival rate was reported at 8.4 months, compared to 5.3 months with temozolomide.

The safety profile of paxalisib was similar to that observed in other clinical trials, with hyperglycaemia (high blood sugar), mucositis (mouth ulcers), and rash among the most common toxicities.

Angiogenesis drug

Kazia’s second drug, EVT801, commenced recruitment to a phase one study in November at the Oncopole cancer research centre in Toulouse, France.

In January, recruitment also started at cancer care and research hospital Centre Leon Berard in Lyons.

The study will examine the safety, tolerability and pharmacokinetics of EVT801 administered as monotherapy, using a ‘dose escalation’ design.

Once a maximum tolerated dose is determined, Kazia will enrol additional patients in two distinct populations (renal cell carcinoma and soft tissue sarcoma) to clarify the drug’s clinical activity.

The phase one study has been designed to incorporate a range of translational biomarkers and is expected to provide valuable data on the pharmacological activity of EVT801 in patients with cancer.

At the end of January, the study had cleared the first dose level and had begun treatment at the second dose.

Licencing deal

Kazia brought EVT801 into its portfolio in April, following a $496 million licencing deal with drug development company Evotec SE whereby Kazia would take the drug through clinical trials and onto commercialisation.

Research shows that growing tumours require an extensive network of newly-formed blood and lymphatic vessels to satisfy their substantial nutrient requirements.

Drugs which inhibit the formation of new blood vessels (angiogenesis inhibitors) have proven effective in suppressing a range of solid tumours; however, their usage can be limited by treatment resistance caused by low oxygen levels in the tumour, and by toxicity.

EVT801 has been designed to selectively target lymphangiogenesis (the formation of new lymphatic vessels) and is expected to provide many of the same benefits as inhibition of angiogenesis, minus the resistance and toxicity.

Childhood brain cancer study

In November 2021, the Pacific Paediatric Neuro-Oncology Consortium (PNOC) began recruitment to an adaptive phase two study of multiple drug candidates for the treatment of diffuse midline gliomas (DMGs) in children, including diffuse intrinsic pontine glioma (DIPG).

DIPG is a rare and aggressive brain cancer for which there are no current FDA-approved treatments, and, in which, the median overall survival rate is less than one year.

The PNOC study is designed to investigate a combination of therapies in the treatment of DIPG, including paxalisib with investigational drug ONC201 manufactured by US-based biopharmaceutical company Chimerix Inc.

The potential use of paxalisib in DIPG has been extensively studied by leading Australian cancer researcher, Professor Matt Dun, at the Hunter Medical Research Institute. Professor Dun has trialled paxalisib in cutting edge laboratory experiments, and has reported highly encouraging results.

In August 2020, Kazia received Orphan Drug Designation (ODD) and Rare Paediatric Disease Designation (RPDD) from the US FDA for this patient population.

Successful year

Kazia chief executive officer Dr James Garner said the company’s December quarterly performance capped off a successful year.

“Our fundamentals remain very strong, with two high-quality assets in human trials and cash through to fourth quarter of CY2022,” he said.

“Our areas of focus this year will include the important work of preparing paxalisib for potential commercialisation, and driving what may be transformative data from the broad clinical program that is underway across both our drug candidates.”