FDA to Discuss Paxalisib Registration Pathways for Glioblastoma with Kazia Therapeutics
核心洞察
The FDA has granted Kazia Therapeutics (搜索) a Type C meeting to discuss potential registration pathways for paxalisib in newly diagnosed glioblastoma (搜索).
Paxalisib demonstrated a statistically significant improvement in overall survival in patients with unmethylated glioblastoma (搜索) in the GBM AGILE trial.
Prior phase 2 study results showed paxalisib yielded positive safety and efficacy outcomes compared to temozolomide in newly diagnosed glioblastoma (搜索).
Kazia Therapeutics (搜索) will meet with the FDA to discuss the registration of paxalisib as a treatment for newly diagnosed glioblastoma (搜索). The Type C meeting was granted to discuss potential pathways for paxalisib (GDC-0084), an investigational brain-penetrant inhibitor of the PI3K/mTOR (搜索) pathway, in this patient population.
Promising Results from GBM AGILE Trial
Data from the phase 2/3 GBM AGILE trial (NCT03970447) may support the viability of paxalisib. Prespecified secondary analysis results from GBM-AGILE showed that paxalisib meaningfully improved overall survival (OS) among patients with unmethylated glioblastoma (搜索). The full data from the trial, including outcomes related to secondary end points from the paxalisib arm, are anticipated to be presented at a scientific meeting later this year.
Previous results from the GBM-AGILE clinical trial showed a boost in OS with paxalisib at 15.54 months vs 11.89 months with concurrent standard-of-care (SOC) therapy among patients with unmethylated disease. No new safety signals were associated with paxalisib.
"We are excited to have shown a 3.8 month improvement in [OS], an approximate 33% improvement, for [patients with] newly diagnosed unmethylated [glioblastoma (搜索)] compared [with] the concurrent [SOC] arm," said John Friend, MD, chief executive officer at Kazia Therapeutics (搜索).
Prior Phase 2 Study Demonstrates Efficacy
In 2021, preliminary findings from a phase 2 study (NCT03522298) trial showed that paxalisib yielded positive results for the drug’s safety and efficacy profile in glioblastoma (搜索) compared with temozolomide (Temodar). The median OS was 15.7 months (95% CI, 11.1-19.1) with paxalisib across the intent-to-treat population vs a historical median of 12.7 months with temozolomide in this patient group. Additionally, the median progression-free survival (PFS) was 8.4 months (95% CI, 6.6-10.2) with paxalisib vs a historical median of 5.3 months with temozolomide. The safety profile of paxalisib in the trial was comparable with prior reports of the agent. Common agent-related toxicities included hyperglycemia, oral mucositis, and skin rash.
Ongoing and Prior Regulatory Designations
Additional trials involving paxalisib in brain metastases (搜索), diffuse midline gliomas (搜索), and primary central nervous system lymphoma (搜索) are currently underway and showing encouraging interim data. Paxalisib had been granted orphan drug status by the FDA in 2018, as well as fast track status by the FDA in 2020, to operate as a first-line treatment for patients with glioblastoma (搜索) with unmethylated MGMT promoter status following radiation plus temozolomide therapy.
Paxalisib also received fast track designation in July 2023 for the treatment of patients with solid tumor brain metastases (搜索) that harbor PI3K pathway mutations in combination with radiation therapy. Additionally, it earned rare pediatric disease designation and orphan drug designation by the FDA for diffuse intrinsic pontine glioma (搜索) in August 2020, and for atypical teratoid (搜索) and rhabdoid tumors (搜索) in June 2022 and July 2022, respectively.