NeoPharm, Inc. announced that the independent Data Monitoring Committee (DMC) responsible for overseeing the cintredekin besudotox (IL13-PE38QQR) pivotal phase III Precise Trial for the treatment of glioblastoma multiforme (GBM) has analyzed the data from the trial's interim efficacy analysis (160 deaths) and has recommended that the trial continue to the final efficacy analysis at 215 deaths. The DMC's role was to conduct the interim analysis to determine if efficacy could be proven early, or to proceed to the final efficacy analysis at 215 deaths.
"We knew that reaching the interim efficacy endpoint was an extremely high statistical hurdle and we look forward to the final study endpoint, which we currently expect to occur in the first quarter of 2007," said Guillermo A. Herrera, president and chief executive officer of NeoPharm. "We continue to be encouraged by the previously reported prolonged survival times observed in the phase I/II trials and view these prolonged survival times as providing evidence that the Precise Trial milestones will eventually be achieved. Our trial investigators continue to be encouraged about our chances for a positive outcome for the trial. Based on this, we continue to be optimistic about obtaining a positive final study outcome."
The final efficacy analysis of the Precise trial will be based on the comparison of the overall patient survival curves of the two treatment groups. If there is a statistically significant difference, or separation, in the overall survival curves of besudotox and Gliadel, then the Precise trial will have met its endpoint. In order to reach statistical significance at the Final Efficacy analysis, the survival advantage for cintredekin besudotox over Gliadel Wafer must achieve a p-value of less than or equal to 0.048 versus the p-value of less than or equal to 0.005 required to reach statistical significance at interim efficacy analysis.
"I remain confident in the potential of cintredekin besudotox to treat this dismal disease, based on the median survival results observed to date in the phase I/II studies," said Sandeep Kunwar, MD, Associate Professor of Neurological Surgery, University of California at San Francisco (UCSF) and principal investigator of the Precise trial.
Glioblastoma multiforme (GBM) is the most common type of malignant primary brain tumour in adults. According to the Central Brain Tumour Registry of the United States (www.cbtrus.org), GBM tumours usually affect men more commonly than women, particularly men between the ages of 60 and 85 years. According to the CBTRUS, approximately 10,000 people are diagnosed annually with malignant glioma (GBM and anaplastic astrocytoma) and this disease is eventually fatal for most patients. Survival time for GBM patients ranges from six months for recurrent disease to 12 months with newly diagnosed disease despite aggressive treatments including surgery, radiation therapy and chemotherapy.
GBM tumours mainly arise in the cerebral hemispheres (the main portions of the brain), but they can also occur in the brainstem, cerebellum, or spinal cord. Symptoms of a GBM can include headaches that are caused by increased intracranial pressure, neurological deficits such as weakness, sensory loss, coordination difficulties, visual impairment, cognitive impairment affecting memory and language, seizures, and personality changes.
Cintredekin besudotox is a recombinant protein consisting of a single molecule composed of two parts: a tumour-targeting molecule (Interleukin-13 or IL13) and a cytotoxic agent (Pseudomonas Exotoxin, or PE38). IL13 receptors are present in appreciable numbers on malignant glioma cells, but only to a minimal amount if at all on healthy brain cells. The IL13 portion is designed to bind to receptors on tumour cells like a key fits into a lock. The cancer cell appears to latch onto and absorb the IL13 and the attached PE38, causing destruction of the cancer cell. Healthy brain cells appear to be unharmed because they do not internalize the PE. The drug is delivered via Convection Enhanced Delivery (CED), a novel drug delivery system using catheters placed following tumour resection (removal), in areas with microscopic tumour spread or at risk of tumour spread around the tumour resection cavity.
Cintredekin besudotox has received Orphan Drug designation and Fast Track designation from the U.S. Food and Drug Administration (FDA). Cintredekin besudotox was also accepted into FDA's Pilot 2 Program for continuous marketing applications. Cintredekin besudotox has also received Orphan Drug designation in Europe.