Glioblastoma multiforme (GBM) is a grade IV tumor that arises from astrocytes. It is the most common and aggressive human brain tumor, accounting for 15.4% of all primary brain tumors and 60-75% of all astrocytomas. It has a peak incidence between 55 and 84 years of age, with the median age of diagnosis being 64 years. In the US and EU, the annual incidence was estimated to be three to four cases per 100,000 people. GBM has a high degree of intratumoral heterogeneity, which is associated with poor prognosis and the development of drug resistance.
The GBM market is characterized by a small selection of marketed product options, consisting of chemotherapies, cancer immunotherapies and receptor tyrosine kinase inhibitor products. The pipeline is moderately large, with 512 products active across all stages of development. First-in-class products only constitute approximately a quarter of the pipeline, and represent 31% of products with a disclosed target. The most widely studied group of first-in-class targets are the receptor tyrosine kinase and ligand inhibitors, a trend that has been heavily influenced by the success of Avastin, and possibly successful EGFR inhibitors such as Tarceva that are used in the treatment of other oncology indications.
Potential driving factors for the market include a typically poor outcome for treated patients, a growing patient pool if disease prognosis can be improved, a lack of approved options in the market, and a strong understanding of the disease pathophysiology that has developed over the last decade, facilitating the development of novel compounds that may fulfill the unmet needs.
Overall, due to the highly complex and polygenic nature of GBM, which has numerous subtype classifications, it is unlikely that the inhibition of a single target will be sufficient to substantially improve patient prognosis. Instead, it is more likely that the concurrent use of multiple targeted therapies, along with other available modes of therapy, may improve treatment outcomes. First-in-class targets analyzed in this report have shown encouraging efficacy profiles, and some show the ability to chemosensitize cancer cells.
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