Dr Asa Abeliovich, MD, PhDAsa Abeliovich, MD, PhD
The FDA has granted fast track designation to PR001, an investigational, disease-modifying, single-dose AAV9-based gene therapy for treatment of Parkinson disease with a mutation in the glucocerebrocidase-1 (GBA1) gene, according to Prevail Therapeutics.

In June, the FDA accepted the company’s investigational new drug application which allows for the initiation of a phase 1/2 clinical trial that will examine the safety and tolerability of PR001. The trial will also measure key biomarkers and exploratory efficacy endpoints in patients with Parkinson disease with GBA1 mutation. Dosing is expected to occur in the second half of 2019.1

“We are pleased that the FDA has granted fast track designation for PR001, which underscores the unmet need of patients with Parkinson disease with GBA1 mutation, a chronic and progressive neurodegenerative disorder that comprises 7% to 10% of the total Parkinson disease population worldwide,” Asa Abeliovich, MD, PhD, founder and chief executive officer, Prevail, said in a statement.2 “With no treatments available that modify the progressive course or the underlying disease process of Parkinson disease, a potential disease-modifying therapy like PR001 could significantly transform the lives of patients with this disease.”

In the preclinical program in both mouse models and non-human primates, PR001 was reported to be well tolerated and demonstrated robust and widespread biodistribution. Investigators observed significant increases in enzyme activity, reduction in lipid accumulation, and improvements in motor function.3

In a dose-finding study, 3 separate doses of PR001 were administered to CBE mice by intracerebroventricular injection. The low dose was 3.2 x 109 vg; the medium dose was 1 x 1010 vg; and the high dose was 3.2 x 1010 vg; and at all 3 doses, vector genomes were detected in the brain and spinal cord 5 weeks postadministration. It was observed that GCase activity was reduced in CBE-treated mice and increased by the highest dose of the therapy in the brain and spinal cord at 5 weeks.3

“We are pleased that the FDA has accepted the IND for our first program, which we believe has the potential to transform the lives of patients with Parkinson disease with a GBA1 mutation,” Abeliovich explained.1 “At Prevail, our goal is to halt the progression of serious neurodegenerative diseases by applying precision medicine to the development of gene therapies. Our active IND brings us a step closer to achieving that goal, and we look forward to entering this new phase as a clinical-stage company.”

PR001 is also in development for the treatment of neuronopathic Gaucher disease.
REFERENCE
1. Prevail Therapeutics Announces IND Active for Phase 1/2 Trial of its Gene Therapy PR001 to Treat Parkinson’s Disease Patients with GBA1 Mutations [news release]. New York: Prevail Therapeutics; June 4, 2019. https://www.businesswire.com/news/home/20190604006119/en/Prevail-Therapeutics-Announces-IND-Active-Phase-12. Accessed July 9, 2019.

2. Prevail Therapeutics Receives U.S. FDA Fast Track Designation for PR001 for the Treatment of Parkinson’s Disease Patients with a GBA1 Mutation [news release]. New York: Prevail Therapeutics; July 8, 2019. https://finance.yahoo.com/news/prevail-therapeutics-receives-u-fda-120000856.html. Accessed July 9, 2019.
3. United States Securities and Exchange Commission. Form S-1 Registration Statement. Prevail Therapeutics Inc. https://www.sec.gov/Archives/edgar/data/1714798/000119312519157078/d673777ds1.htm#tx673777_1. May 24, 2019. Accessed July 9, 2019.