San Antonio-based Genspera Inc., providers of state-of-the-art technologies in biomedical science in the field of cancer therapy, recently announced the enrollment of their first patient for the phase II clinical trials of their premier pipeline drug G-202. The company’s new drug is being tested as a therapy for Glioblastoma Multiforme (GBM) — a common form of brain tumor with very low survival rates. The trial will be conducted at the UC San Diego Moores Cancer Center, led by its principal investigator, Dr. David Piccioni, MD, PhD.
GBM is an aggressive and malignant form of tumor that involves abnormal division of neuroglial cells accompanied by angiogenesis (uncontrolled division of blood vessels). It has very low survival rates (median overall survival of only 4 months without treatment) and accounts for 52% of all functional tissue brain tumor cases. No definitive treatment for GBM exists to date, with common treatment options being chemotherapy, radiation, and surgery. According to the American Association of Neurological Surgeons, none of the regimens undertaken to treat GBM are curative. Hence, there is always a need for therapeutic agents as part of viable treatment regimens.
G-202 works on the basis of a Mediterranean plant-derived cytotoxin called Thapsigargin, modified to form 12ADT [ 12 (Aminododecanoyl)-8-O-DebutanoylThapsigargin ]. This compound is added to a non-toxic pro-drug delivery system and injected intravenously. The enzyme PSMA (Prostrate Specific Membrane Antigen), found in high concentration in almost all types of tumor cells, especially brain and liver, is an activator for G-202. Upon activation, G-202 is hydrolyzed into the toxic form 12-ADT-Asp, which causes accumulation of calcium in the cytosol and lead to apoptosis (cell death). It is by stopping the nutrient supply for the malignant cells, does G-202 exert its effect. As a result, it is considered as a potential therapeutic agent for most tumors.
The trial is expected to treat up to 34 patients who have already been diagnosed or have had the persistent condition even after one form of treatment or the other.
Speaking about this, Dr. Piccioni said, “We are excited to open this clinical trial using a novel tumor-targeting technology in recurrent glioblastoma patients with the goal of improving survival and identifying biomarkers of response.”
Dr. Santosh Kesari, MD, PhD, co-investigator, neuro-oncologist and director of the Translational Neuro-Oncology Laboratories at UC San Diego Moores Cancer Center, also expressed his views regarding the trial, saying “Researchers at the UC San Diego School of Medicine are focused on creating improved therapies for brain cancer patients. As such, we were one of the first to show robust expression of PSMA in the vasculature of glioblastomas, as well as in other gliomas, which formed the rationale to proceed with G-202 in a GBM clinical trial.”
Genspera’s Craig Dionne, PhD and CEO, was quoted saying “The GBM trial constitutes another milestone in our plan to develop G-202 in multiple cancer indications. We are particularly pleased to collaborate with Dr. Kesari and his colleagues, who have been so instrumental in developing the rationale for potential utility of G-202 in GBM and other brain tumors.”