FDA Grants Fast Track Designation to Paxalisib for Patients with Glioblastoma

August 20, 2020

The FDA granted fast track designation to paxalisib for the treatment of patients with newly diagnosed glioblastoma with unmethylated O6-Methylguaninemethyltransferase promoter status who have completed initial radiation with concomitant temozolomide.

The FDA has granted fast track designation to paxalisib for the treatment of patients with newly diagnosed glioblastoma with unmethylated O6-Methylguaninemethyltransferase (MGMT) promoter status who have completed initial radiation with concomitant temozolomide (Temodar), according to Kazia Therapeutics, the developer of the agent.1

This indication reflects the patient population currently being studied by Kazia in an ongoing phase 2 study and is also the primary proposed population for the GBM AGILE pivotal study, which is anticipated to begin in the second half of 2020. Additionally, it is the intended indication for commercial launch.

“In awarding fast track designation to paxalisib, [the] FDA has recognized the drug’s potential to meaningfully improve outcomes for patients with glioblastoma. This is a very powerful acknowledgement,” James Garner, MBBS, Kazia CEO, said in a press release. “We look forward to working closely with FDA as we move into the final stage of development for paxalisib.”

Kazia completed recruitment for its phase 2 clinical trial of paxalisib in newly diagnosed glioblastoma in February 2020, and interim clinical data was presented at the American Association of Cancer Research (AACR) Virtual Annual Meeting II in June 2020.2 

Overall survival (OS) was calculated at 17.7 months, which compares favorably to the previously reported figure of 12.7 months for temozolomide, the existing FDA-approved standard of care. Moreover, a median progression-free survival (PFS) of 8.5 months was also determined for the entire study population. Importantly, as of May 2020, 1 patient remains progression-free and on treatment 22 months after diagnosis.

The company plans to present further data from this study in the second half of 2020 and should conclude the study in early 2021.

Phase 1 studies of paxalisib are also underway in diffuse intrinsic pontine glioma (DIPG) and diffuse midline gliomas (DMGs) (NCT03696355), and in brain metastases in combination with radiotherapy (NCT04192981). Additional phase 2 studies are also in progress in brain metastases (NCT03994796) and in HER2-positive breast cancer brain metastases (NCT03765983). Studies in other forms of brain cancer are currently under discussion.

Notably, paxalisib was granted orphan drug designation for glioblastoma by the FDA in February 2018. In addition, the agent was granted rare pediatric disease designation by the FDA in August 2020 for DIPG.

References:

1. US FDA AWARDS FAST TRACK DESIGNATION (FTD) TO PAXALISIB FOR GLIOBLASTOMA [news release]. Sydney. Published August 20, 2020. Accessed August 20, 2020. https://kza.irmau.com/irm/PDF/ac5fb302-d6b2-4cc0-9722-ec13653d71c5/Kazia39spaxalisibgrantedFastTrackDesignationbyFDA

2. Wen PY, de Groot J, Battiste JD, et al. Phase 2a study to evaluate the safety, pharmacokinetics, and clinical activity of the PI3K / mTOR inhibitor paxalisib (GDC-0084) given to glioblastoma (GBM) patients with unmethylated MGMT promotor status. Presented at the AACR Virtual Annual Meeting II in June 2020. Poster number: CT205.