Oncology-focused, clinical-stage biotech company Kazia Therapeutics (ASX: KZA) reported strong progress in the development of its lead drug candidates in the three months to Dec. 31.
Work has focused on studies for the treatment of brain cancer with paxalisib, in particular the international GBM AGILE study in glioblastoma conducted by the Global Coalition for Adaptive Research.
The study already has several dozen sites underway in the United States and was opened to Canadian hospitals in November, with the first site being Sunnybrook Health Sciences Center in Ontario.
Additional sites are being rolled out.
Approval of a new drug
In December, Kazia and Chinese company Simcere Pharmaceutical were informed that an investigational new drug application for paxalisib in China had received regulatory approval.
The approval is a critical step in the launch of GBM AGILE in China and the potential pursuit of further paxalisib clinical trials.
The study is expected to open for recruitment in China by mid-year.
The GBM AGILE study initially focused on the United States, which now includes more than 40 major cancer hospitals.
It uses a sophisticated and innovative approach called “adaptive design” to readjust its statistical power over time. This approach has the potential to significantly speed up lead times and reduce costs.
If an answer becomes clear after fewer than 200 patients, the study will end early and Kazia will use the final data to submit a New Drug Application to the US Food and Drug Administration (FDA).
Paxalisib Phase 2 Study
In December, Kazia announced the first positive final data from its own Phase 2 study of paxalisib in patients with newly diagnosed glioblastoma.
The study reported a median overall survival rate of 15.7 months in people treated with paxalisib, compared with 12.7 months with the existing standard treatment, 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 seen in other clinical trials, with hyperglycemia (high blood sugar), mucositis (mouth ulcers), and rash among the most common toxicities .
Kazia’s second drug, EVT801, began recruiting for a phase one study in November at the Oncopole cancer research center in Toulouse, France.
In January, recruitment also began at the Léon Bérard oncology care and research hospital center in Lyon.
The study will examine the safety, tolerability and pharmacokinetics of EVT801 administered as monotherapy, using a “dose escalation” design.
Once a maximum tolerated dose has been determined, Kazia will enroll additional patients in two distinct populations (renal cell carcinoma and soft tissue sarcoma) to clarify the clinical activity of the drug.
The phase one study was designed to incorporate a range of translational biomarkers and is expected to provide valuable data on the pharmacological activity of EVT801 in cancer patients.
By the end of January, the study had cleared the first dose level and started treatment on the second dose.
Kazia introduced EVT801 to its portfolio in April, following a $496 million licensing deal with drug development company Evotec SE, under which Kazia would take the drug through clinical trials and up to to its marketing.
Research shows that growing tumors require an extensive network of newly formed blood and lymph vessels to meet their substantial nutrient needs.
Drugs that inhibit the formation of new blood vessels (angiogenesis inhibitors) have been shown to be effective in suppressing a range of solid tumours; however, their use may be limited by resistance to treatment caused by low oxygen levels in the tumor and by toxicity.
EVT801 was designed to selectively target lymphangiogenesis (the formation of new lymphatic vessels) and should provide many of the same benefits as angiogenesis inhibition, minus resistance and toxicity.
Childhood Brain Cancer Study
In November 2021, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) began recruitment for an adaptive phase two study of several 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 is currently no FDA-approved treatment and for 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 the investigational drug ONC201 manufactured by US biopharmaceutical company Chimerix Inc.
The potential use of paxalisib in DIPG has been extensively investigated by Australia’s leading cancer researcher, Professor Matt Dun, at the Hunter Medical Research Institute. Professor Dun has tested paxalisib in state-of-the-art laboratory experiments and reported very encouraging results.
In August 2020, Kazia received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) from the US FDA for this patient population.
Kazia’s chief executive, Dr. James Garner, said the company’s quarterly performance in December capped off a successful year.
“Our fundamentals remain very strong, with two high quality assets in human trials and liquidity through the fourth quarter of CY2022,” he said.
“Our areas of focus this year will include the important work of preparing paxalisib for potential commercialization and driving what could be transformative data from the extensive clinical program underway for our two drug candidates.”