FDA Grants ODD to Paxalisib for Rare Pediatric Brain Cancer


Paxalisib has been granted orphan drug designation by the FDA for the treatment of patients with atypical rhabdoid or teratoid tumors in rare and aggressive childhood brain cancer.

The FDA has granted an orphan drug designation (ODD) to paxalisib (GDC-0084), for the treatment of patients with atypical rhabdoid or teratoid tumors (AT/RT) in rare and aggressive childhood brain cancer, according to Kazia Therapeutics Limited.1

If Kazia Therapeutics seeks approval for this indication, the FDA will waive fees for a future regulatory filling in AT/RT.

"Childhood brain cancer has emerged as an important area of focus for the paxalisib program. We have been working for some years with several world-leading researchers in DIPG, one of the most aggressive childhood cancers. Recent data presented at the AACR conference by Dr Jeffery Rubens and colleagues from Johns Hopkins Medical School has shown the potential of the drug to also add benefit in AT/RT,2 another form of childhood brain cancer that is very poorly served by existing treatments. This represents an important new opportunity for paxalisib, and one that we continue to explore enthusiastically with our collaborators and advisors,” stated James Garner, MD, chief executive officer of Kazia Therapeutics, in the press release.

Paxalisib was granted an ODD for the malignant glioma indication, which includes glioblastoma in adults and diffuse intrinsic pontine glioma (DIPG) for pediatric patients. The Pacific Pediatric Neuro Oncology Consortium is currently leading a phase II study for the DIPG indication.

In the phase II clinical trial (NCT05009992) which includes paxalisib, multiple drug therapies in diffuse midline gliomas (DMGs), including DIPG are being tested.

This study has an estimated enrollment of 216 patients who will be randomized to receive 1 of 3 treatment regimens involving combinations of radiation therapy, the drug ONC201, and paxalisib.

The primary end point of the study is progression-free survival (PFS) at 6 months and overall survival (OS) at 7 months. Exploratory end points include confirming the blood brain barrier penetration of ONC201 in DMG, assessing changes in immune cell infiltration in DMG tumor tissue, and toxicity.

Initial data of this study is expected sometime during 2023.3

Another study of paxalisib in DIPG is nearing completion. This is a phase 1 study (NCT03696355) led by St Jude’s Children’s Research Hospital in Memphis, TN.

The trial consists of a dose escalation phase where patients will receive paxalisib in doses of 21 mg/m2, 27 mg/m2, 35 mg/m2, or 45 mg/m2 after completion of radiation therapy.

The primary end point of this study is to estimate the maximum tolerated dose and the recommended phase 2 dose paxalisib after standard radiation therapy. Secondary end points include overall response, duration of best overall response, PFS, and OS Data from this trial is expected to be published at the end of 2022.4

Kazia Therapeutics will be participating in a webinar to discuss the company’s activities concerning childhood brain cancer on Wednesday, June 22, 2022.

1. US FDA awards orphan drug designation (ODD) to paxalisib for AT/RT, a rare form of childhood brain cancer. Press release. BioSpace; June 17, 2022. Accessed June 20, 2022. https://bit.ly/3A5VicX
2. Malebranche K, Findlay T, Eberhart C, Raabe E, Rubens J. The PI3K inhibitor paxalisib combines synergistically with the pan-Raf inhibitor TAK580 (DAY 101) to extend survival in orthotopic xenograft models of atypical teratoid/rhabdoid tumors. Presented at the 2022 American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Accessed June 20, 2022. https://bit.ly/3OuVExl
3. Combination therapy for the treatment of diffuse midline gliomas. ClinicalTrials.gov. Updated June 9, 2022. Accessed June 20, 2022. https://clinicaltrials.gov/ct2/show/record/NCT05009992?term=NCT05009992&draw=2&rank=1
4. Study of GDC-0084 in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma or diffuse midline gliomas. ClinicalTrials.gov. Updated March 24, 2022. Accessed June 20, 2022. https://clinicaltrials.gov/ct2/show/record/NCT03696355?term=NCT03696355&draw=2&rank=1
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