FDA Accelerates Testing and Review of Experimental Brain Cancer Drug

An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing. 

Breakthrough status is designed to speed the development and approval of candidate therapies that treat serious or life-threatening diseases and show early evidence of outperforming existing treatments. 

After years of testing, the FDA finally granted approval to test the therapy on humans.

The ruling comes in response to an application from a Duke University research group for a drug (PVS-RIPO) that uses a modified polio virus to fight glioblastoma, the most common and most lethal brain cancer. The incidence of glioblastoma multiforme in the United States is 2 to 3 per 100,000 people, mainly among those aged 45 to 70, according to the National Cancer Institute (NCI). Patients typically succumb to the disease in the first 15 months after diagnosis. 

The Biopharmaceutical Development Program (BDP) at the Frederick National Lab has been supporting Duke University Medical Center by manufacturing the drug for clinical testing. The BDP has produced enough of the therapy for about 1,500 patients. 

"We are doing things no one else will or can do," said Doug Gaum, Director of Quality Assurance, BDP. 

Mathias Gromeier, M.D., Professor, Department of Neurosurgery, Duke University School of Medicine, is an expert on glioblastoma and polio virus. He re-engineered the Sabin vaccine strain of the polio virus so it would attack malignant cells but not harm normal cells. 

According to the Preston Robert Tisch Brain Tumor Center at Duke, cancer-fighting viruses must target cancer cells for infection and kill them. Only a few viruses are eligible cancer-fighting agents. Scientists used genetic engineering to remove the polio virus' disease-causing ability. Because the receptor that PVS-RIPO binds to is present on most solid tumor cells, it naturally infects most solid tumors. After years of preclinical testing, the FDA approved the first human clinical trials. 

News reports have focused on the case of Stephanie Lipscomb, a nursing student who was only 20 when she was diagnosed with stage-four glioblastoma. She went through surgery, but the tumor returned within two years. At age 22, she was the first patient to enter the PVS-RIPO clinical trial. At first, the tumor looked worse due to inflammation. But then it began to shrink. Three years later, an MRI showed no evidence of the cancer. 

Fritz Anderson, a 70-year-old retired cardiologist who failed all other forms of standard therapy, was the second success story of the polio trial and has also appeared in news stories. Phase I clinical trials are intended to find the proper dosage, not cure patients. But Anderson told CBS News, "I feel it is a cure and I live my life that way." 

After these successes, the research group tripled the dosage, but this resulted in life-threatening brain inflammation so they reduced the dosage to about one-tenth of the amount that Lipscomb and Anderson received. The phase I trial is ongoing. 

Scientists have found that the receptor that PVS-RIPO binds to is found on various tumors in addition to glioblastoma. The virus appears to kill breast, colorectal, liver, lung, pancreatic, prostate, and renal cancer tumors in-vitro. Clinical trials with PVS-RIPO would have to be performed for each of these forms of cancer to determine whether the treatment is clinically useful for any of these tumor types. 

Last updated: November 16, 2016