FDA Grants Fast Track Designation to Paxalisib in Glioblastoma

The FDA has granted a Fast Track designation to paxalisib (formerly GDC-0084) for the treatment of patients with newly diagnosed glioblastoma with unmethylated MGMT promotor status who have completed initial radiation and temozolomide, announced Kazia Therapeutics in a press release.¹

The company is planning to submit a New Drug Application for paxalisib in 2021.

Paxalisib is a small molecule inhibitor of the PI3K, AKT, and mTOR pathways. The Fast Track designation will expedite the development of this potential treatment in order to address the unmet medical need for better treatment options. The company will collaborate with the FDA as they continue to develop paxalisib.

“In awarding Fast Track Designation to paxalisib, FDA has recognized the drug’s potential to meaningfully improve outcomes for patients with glioblastoma. This is a very powerful acknowledgement,” said James Garner, MD, chief executive officer, Kazia, in a statement. “The opportunities that Fast Track Designation creates, as we move towards a New Drug Application filing, are of great value and have the potential to substantially accelerate the commercialization of paxalisib. In particular, the ‘rolling review’ process enables Kazia to complete and submit substantial sections of our NDA filing in advance, saving time and reducing risk for the product. We look forward to working closely with FDA as we move into the final stage of development for paxalisib.”

The company completed recruitment for a phase 2 clinical trial of paxalisib as treatment of patients with newly diagnosed glioblastoma in February 2020. The interim clinical data were also presented during the American Association of Cancer Research (AACR) Virtual Annual Meeting II.

According to these results, the median overall survival (OS) was 17.7 months in the 9 patients enrolled in part A of the study, which compared favorably to the historical median OS of 12.7 months with the current standard of care, temozolomide. These study data demonstrated an early positive OS signal in patients with glioblastoma.²

In a slightly larger group of 30 patients, the median progression-free survival was 8.5 months, which again compared favorably with the historical median of 5.3 months with temozolomide.

Of the 30 total patients enrolled in this study, 9 were in part A, the dose-escalation cohort, and 21 were in part B. The OS analysis only included the patients from cohort A, while the progression-free survival analysis included all 30 evaluable patients from both parts of the study.

The 1 patient who had received the longest duration of treatment remained progression-free at 19 months, and about half the patients in the study had remained on treatment.

No major safety signals were observed in this study. The most common adverse events included hyperglycemia, oral mucositis, and low-grade rash.

Further results from this clinical trial are expected to be presented in the second half of 2020, and the final results in early 2021. The agent has also been selected to join the international GBM AGILE study in glioblastoma, of which recruitment is expected to begin in the second half of 2020.¹

Four other studies of paxalisib remain ongoing in other forms of brain cancer, and the agent has also received an Orphan Drug designation for the treatment of glioblastoma in February 2018. Additionally, the agent was granted Rare Pediatric Disease designation by the FDA in August 2020.

_References

_{1. US FDA awards Fast Track Designation (FTD) to paxalisib for glioblastoma. News Release. Kazia Therapeuitics Limited. August 20, 2020. Accessed August 20, 2020. https://bit.ly/3kWKQud}

_{2. Kazia's paxalisib shows positive overall survival signal in phase II glioblastoma study. News release. Kazia Therapeutics Limited. April 7, 2020. Accessed August 20, 2020. https://yhoo.it/2JP8QOA}