Press Release: FDA Grants Orphan Drug Designation for PVSRIPO for the Treatment of Advanced Melanoma
Istari Oncology Announces FDA Grants Orphan Drug Designation for PVSRIPO for the Treatment of Advanced…
Istari Oncology, Inc., a clinical-stage biotechnology company focused on novel immuno-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors, announced today publication of the results of a Phase 1 trial of PVSRIPO in recurrent glioblastoma in The New England Journal of Medicine (NEJM). This trial was conducted by The Preston Robert Tisch Brain Tumor Center at Duke.
In this trial of 61 adult patients, overall survival at 24 and 36 months was 21%, compared to 14% at 24 months and 4% at 36 months in matched historical controls. Three patients receiving PVSRIPO have survived beyond 60 months.
“The impressive results with PVSRIPO in this trial are the best we have seen to date in patients with recurrent glioblastoma and provide hope for these patients whose typical survival time is less than a year,” said Henry S. Friedman, MD, Chief Medical Officer of Istari and James B. Powell, Jr. Professor of Neuro-Oncology and the Division Chief for Neuro-Oncology in The Preston Robert Tisch Brain Tumor Center in the Department of Neurosurgery at Duke. “Based on the observation that the receptor for PVSRIPO, CD155, is present on almost all solid tumors, we look forward to future trials in other cancers, as well as glioblastoma, both alone and in combination with other agents, as we strive to provide hope for these patients as well.”
The primary objective of the Phase 1 study was to determine the toxicity profile and Phase 2 dose for intratumoral convection enhanced delivery of PVSRIPO in WHO grade IV malignant glioma (glioblastoma). The secondary objective was to estimate overall survival compared to an historical control group. From May 2012 to May 2017, 61 consecutive adult patients with recurrent WHO grade IV malignant glioma with measurable disease were enrolled in the study that evaluated seven doses. The median overall survival for all 61 PVSRIPO patients was 12.5 months compared to 11.3 months for the matched historical control group. However, the overall survival of PVSRIPO patients reached a plateau beginning at 24 months with 24- and 36-month overall survival of 21%, while the overall survival in the matched historical control continued to decline with 24-month overall survival of 14% and 36-month overall survival of 4%. Of these survivors, two patients are beyond 70 months, and one patient is beyond 60 months.
Adverse events affecting more than 20% of patients in the dose-expansion phase included headaches (52%), pyramidal tract syndrome (hemiparesis) (50%), seizure (45%), dysphasia (28%), and cognitive disturbance (25%). The NEJM publication is available at https://www.nejm.org/doi/full/10.1056/NEJMoa1716435?query=featured_home.
A multi-center Phase 2 trial of PVSRIPO alone and in combination with chemotherapy in adults with recurrent glioblastoma is currently enrolling, with a primary endpoint of 24-month survival. A Phase 1 trial of PVSRIPO in pediatric patients with recurrent glioblastoma is also currently enrolling. For additional information on clinical trials with PVSRIPO, please visit https://istarioncology.com/pipeline/clinical-trials/.
Positive preclinical data for PVSRIPO has been generated in multiple solid tumor models, both alone and in combination with other agents, including checkpoint inhibitors. Phase 1 trials are currently planned for PVSRIPO in breast carcinoma and melanoma.
PVSRIPO is the Sabin type 1 polio vaccine, genetically modified so it cannot harm or kill normal cells. PVSRIPO is a prototypic oncolytic recombinant polio virus vaccine that recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of all solid tumors except Burkitt’s lymphoma, and in major immune components of the tumor microenvironment. PVSRIPO has been granted Breakthrough Status and Orphan Status by the FDA.
Glioblastoma is the most common and aggressive form of brain cancer, comprising 52% of patients with primary brain tumors. There are approximately 13,000 patients diagnosed with GBM in the United States annually and approximately 18,000 in the European Union. Despite aggressive treatment, survival for newly diagnosed glioblastoma patients is usually less than 20 months, and for patients with recurrence, which occurs in 98% of patients, survival is usually less than 12 months.
About Istari Oncology
Istari Oncology, Inc., headquartered in Research Triangle Park, North Carolina, is a privately-held clinical-stage biotechnology company focused on novel immuno-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors. The company was founded by Darell Bigner, MD, and Matthias Gromeier, MD, of Duke University Medical Center in 2016. Both are leaders in their respective research fields of virology, immunology, monoclonal development and clinical medicine, particularly in the treatment of brain tumors. Istari licensed a broad range of patents and patent applications from Duke University and has access to additional intellectual property created at Duke to continue clinical and commercial development of these technologies. Our two platforms currently in clinical development are Polio Virus Sabin-Rhinovirus Poliovirus (PVSRIPO) and Antibody-Directed Immuno-Conjugates (ADC). For more information, please visit www.istarioncology.com.
About The Preston Robert Tisch Brain Tumor Center at Duke
Established in 1937, The Preston Robert Tisch Brain Tumor Center was one of the first brain tumor research and clinical programs in the United States. Since then, it has advanced to become one of the best pediatric and adult neuro-oncology programs in the world—leading the way in comprehensive care that combines research breakthroughs, clinical trials and the newest therapies. The National Cancer Institute (NCI) has given the center the highest rating of “outstanding” for each of the last 10 years. For more information please visit https://tischbraintumorcenter.duke.edu/.
Dani P. Bolognesi, PhD
Chief Executive Officer
Timothy J. Creech
Chief Financial Officer