Tanja Obradovic: Advancing repurposing of approved drugs with Avapritinib for high-grade glioma
Tanja Obradovic, Oncology Medical Strategy Advisor at Mercurial AI, shared a post on LinkedIn about a paper by Lisa Mayr et al. published in Cancer Cell:
“Repurposing of the currently approved drugs is receiving substantial attention recently as advances in AI offer improved insight into possibilities.
This development strategy has been recognized for a while as likely wide and efficient opportunity for already marketed drugs that have well defined clinical safety, exposure levels and pharmacological profile so they offer shorter path into wider assessment of the effect upon yet un-explored target/disease.
Very good example of this approach is just published by outstanding teams from the University of Michigan, Dana-Farber Cancer Institute and the Medical University of Vienna.
Work demonstrated signals of Avapritinib effectiveness in patients with high-grade glioma (HGG) who have tumors with DNA alterations in the platelet-derived growth factor receptor alpha (PDGFRA).
Avapritinib is PDGFRA/KIT inhibitor which is already approved by FDA to treat gastrointestinal stromal tumors with a PDGFRA exon 18 mutation as well advanced systemic mastocytosis and indolent systemic mastocytosis.
Work demonstrates high potential for delivering patient benefit from already marketed drugs that can be repurposed, a venue traditionally not vigorously used by originator manufacturers.
Reported study was in a small group of patients (N=8) and it serves as support for the ongoing Rover Phase 1/2 multi-center single-arm study to fully evaluate safety, pharmacokinetics, and efficacy of Avapritinib in pediatric solid tumors with PDGFRA/KIT activating mutations, amplification, or H3K27M DMGs (NCT04773782).
Study added to strong rationale for further clinical evaluation by assessing HGG genomic and transcriptomic evaluation as well as preclinical pharmacology assessment and brain penetration potential for the Avapritinib in addition to initial exploratory clinical testing approach.
This is outstanding result considering dire medical need since surgery and radiation are currently only treatment options and no effective drugs to treat high-grade gliomas, especially upon recurrence. Great news for the HGG patients and validation of the potential for deeper evaluation of already available drugs for new indications.”
“Effective targeting of PDGFRA-altered high-grade glioma with avapritinib”
Authors: Lisa Mayr, Sina Neyazi, Kallen Schwark, Maria Trissal, Alexander Beck, Lukas Chavez,Julia Furtner, Carl Koschmann, Johannes Gojo, Mariella Filbin et al.
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