Paxalisib showed positive and promising results in the phase II trial. (Abstract #2407)
Paxalisib Mechanism of Action: Paxalisib specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in the inhibition of both cell growth and survival in susceptible tumor cell populations.
Kazia Therapeutics provides a complete picture of Phase II data of paxalisib and informative sensitivity analyses as first-line therapy in patients with glioblastoma. The study assessed 30 evaluable patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status; it was a single-arm study in which all patients assessed received paxalisib as a monotherapy. As per the study, the median overall survival was 15.7 months as compared to temozolomide, and in the previously treated patient group, the median overall survival was 12.7 months. Moreover, the median progression-free survival (mPFS) was 8.6 months using the RANO criteria, which shows a substantial increment over 5.3 months associated with temozolomide. In terms of safety, profile paxalisib (Kazia Therapeutics ) was highly consistent with previous clinical studies.
"The new data presented today at ASCO provides a more complete picture of trial, and also includes some informative sensitivity analyses.” –Expert Opinion.
Considering the positive outcomes of paxalisib Phase II data, paxalisib expects a significant shift in the therapeutic paradigm in newly diagnosed glioblastoma patients. However, let’s not forget that GBM is an extremely hard nut to crack, considering the aggressive nature of the disease along with low survival. It has been years since Bevacizumab received approval for Recurrent GBM patients; however, it could not succeed in first-line GBM (except in Japan). However, paxalisib offers more confidence towards safety and tolerability in newly diagnosed glioblastoma patients, which appears to be promising.
The GBM space is seeing some action in the ASCO 2022 with SurVaxM (MimiVax) showing encouraging results and now paxalisib ASCO 2022 showing its potential in the first-line setting. There are other key therapies in development for GBM, such as Regorafenib (Bayer), Durvalumab (MEDIMMUNE/AstraZeneca), and ONC-201 (Chimerix).
Companies- Aivita Biomedical, Inc., Inovio Pharmaceuticals, Denovo Biopharma, IMVAX, Merck Sharp & Dohme Corp. and Eisai, MimiVax, Bristol-Myers Squibb, Novartis Pharmaceuticals