Technological breakthroughs and deeper insights into glioblastoma are revitalizing efforts to tackle this aggressive brain tumor. Companies like Merck, Kazia Therapeutics, CorriXR Therapeutics, and others are leading the charge, raising optimism for patients after years of limited progress.
A Turning Point for Glioblastoma
Glioblastoma multiforme (GBM), while rare, is the most prevalent and aggressive primary brain tumor in adults. With a five-year survival rate below 5%, it remains a formidable challenge. Since the approval of Merck’s temozolomide in 1999, no new effective therapies have emerged, despite significant investment.
John Friend, CEO of Kazia Therapeutics, emphasized the difficulty of developing treatments for glioblastoma. “There have been no truly successful new therapies in over 20 years,” he said.
High-profile failures, including Bristol Myers Squibb’s Opdivo and AbbVie’s Depatux-M, have dissuaded many companies from pursuing glioblastoma treatments. However, renewed interest in neuro-oncology is evident, with promising developments in small molecules, immunotherapies, and gene therapies.
Advances in Small Molecules
Small molecules remain a promising approach due to their established therapeutic potential. Kazia’s paxalisib, an oral small molecule inhibitor targeting the PI3K pathway, is designed to cross the blood-brain barrier (BBB). Data from a Phase II/III study highlighted its efficacy, particularly for patients with unmethylated MGMT protein, a group with the poorest prognosis. Paxalisib improved overall survival by 33% in these patients. Kazia plans to meet with the FDA to discuss approval pathways for newly diagnosed GBM patients.
Merck has also entered the glioblastoma field, acquiring Modifi Biosciences to develop MOD-246, a temozolomide-based small molecule targeting DNA repair pathways. Clinical trials for MOD-246 are expected to begin in 2025.
Black Diamond Therapeutics is pursuing an epidermal growth factor receptor (EGFR) inhibitor, BDTX-1535, aimed at recurrent GBM patients, further expanding the small molecule arsenal.
Cell and Gene Therapies: A New Horizon
Cell and gene therapies are emerging as transformative tools against glioblastoma. Researchers at Penn Medicine are advancing CAR T cell therapies targeting EGFR and interleukin-13 receptor alpha 2. In early trials, tumor size reductions were observed in all treated patients, although neurotoxicity remains a challenge.
CorriXR Therapeutics is exploring gene therapies targeting the NRF2 pathway to combat drug resistance, aiming to dismantle tumors at the DNA level.
Targeting the Immune System
Immunotherapy efforts include therapeutic vaccines designed to enhance the immune response against tumors. Roswell Park Comprehensive Cancer Center’s SurVaxM vaccine has shown promise, doubling overall survival in Phase II trials. Meanwhile, the NCI Neuro-Oncology Branch is developing personalized vaccines derived from patients’ own tumor cells to stimulate immunity post-surgery.
A Growing Market
The glioblastoma treatment market, currently valued at nearly $3 billion, is projected to reach $5.7 billion by 2033, driven by advancements in targeted therapies and immunotherapies.
Deborah Moorad, CEO of CorriXR Therapeutics, believes progress is accelerating. “The technology is catching up, and we’re going to see more investment moving forward. People are being bold,” she said.
With increasing innovation and investment, the long-stalled fight against glioblastoma is gaining momentum, offering new hope to patients and their families.
