The team at Prevail Therapeutics expects to initiate patient dosing in the first half of 2020.
Prevail was awaiting a decision by the FDA to test higher doses of PR001 than initially planned. This request was supported by preclinical evidence of greater efficacy with no safety issues at such dosages. The investigational new drug (IND) application of PR001, an essential step to opening a clinical study, had first been accepted in June 2019.
PR001 uses a modified, harmless version of an adeno-associated virus (AAV9) to deliver a fully working version of the GBA1 gene to nerve cells. Mutations in this gene cause Gaucher disease by producing a defective enzyme called beta-glucocerebrosidase, which leads to the accumulation of fatty molecules inside cells.
In type 2 Gaucher disease, called acute infantile neuronopathic Gaucher disease, these toxic fatty molecules build up in the patient’s brain from early infancy, resulting in neurological symptoms.
By restoring production of normal beta-glucocerebrosidase in affected brain cells, a single dose of PR001 is intended to ease Gaucher symptoms and modify disease course.
Work in mice and monkeys showed that PR001 — now being developed in collaboration with Lonza Pharma & Biotech — is well-tolerated, leads to the production of a functional enzyme in nerve cells, reduces the accumulation of fatty molecules, and improves motor function.
“We are pleased to now have an active IND for PR001 for the nGD [neuronopathic Gaucher disease] indication and look forward to initiating a Phase 1/2 clinical trial in the first half of 2020,” Asa Abeliovich, MD, PhD, Prevail’s founder and CEO, said in a press release.
“Patients with nGD have the most severe form of Gaucher disease and a significant unmet need for therapies to treat their neurological manifestations. We believe PR001 has tremendous potential,” he added.
In addition, the company plans to initiate another Phase 1/2 study in people with type 3 Gaucher later this year. Patients with this type also experience neurological symptoms, but they are milder and progress slower than those seen in patients with type 2 Gaucher.
Prevail is also developing PR001 for GBA1 mutation-related Parkinson’s disease. Mutations in the GBA1 gene are one of the most common genetic risk factors for Parkinson’s. A Phase 1/2 clinical trial (NCT04127578), called PROPEL, is currently recruiting participants with Parkinson’s to test PR001 administered directly into the cerebrospinal fluid (the liquid surrounding the brain and spinal cord).