In October, the FDA placed a clinical hold on the company’s Huntington’s disease gene therapy before that asset could make its way into the clinic.
Jason Armond / Los Angeles Times via Getty Images
Shares of Voyager Therapeutics were down nearly 10% in premarket trading after the company announced the U.S. Food and Drug Administration (FDA) placed a clinical hold on an experimental gene therapy for Parkinson’s disease.
This is the second clinical hold in as many months for Cambridge, Mass.-based Voyager. In October, the FDA placed a clinical hold on the company’s Huntington’s disease gene therapy before that asset could make its way into the clinic.
Late Tuesday, Voyager announced the latest hold. The FDA placed a hold on the RESTORE-1 clinical trial of NBIb-1817 (VY-AADC) after partner Neurocrine Biosciences submitted an Investigational New Drug Safety Report related to the observation of MRI abnormalities in some RESTORE-1 study participants. The clinical implications of this observation are currently unknown and are being evaluated, Voyager said in its announcement.
RESTORE-1 is a Phase II clinical trial assessing NBIb-1817 (VY-AADC), an intracerebral AAV-based investigational gene therapy as a potential treatment of Parkinson’s disease. Voyager said RESTORE-1 Data Safety Monitoring Board (DSMB) has been informed of the clinical hold, as have the study investigators and central and local ethics committees. Neurocrine Biosciences and Voyager will work closely with the FDA and the DSMB to determine the next steps for the RESTORE-1 clinical trial, the company added.
In September, Voyager and Neurocrine announced positive three-year efficacy and safety data in Parkinson’s disease patients who had been treated with VY-AADC. In its announcement, Voyager said patients treated with a one-time dose of the investigational gene therapy, NBIb-1817, showed sustained improvement in motor function including greater “On” time without troublesome dyskinesia, reduction in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III scores and reduction in the amount of medications in patients with Parkinson’s disease.
This is not the first bump in the road for the RESTORE-1 study. The trial had previously been paused due to the ongoing COVID-19 pandemic and was also paused at the request of the independent Data Safety Monitoring Board seeking additional time to review additional data. The DSMB has requested additional patient level data from the trial and now plans to review these data in early 2021, Voyager said in its announcement.
NBIb-1817 is designed to help produce the aromatic L-amino acid decarboxylase (AADC) enzyme in brain cells of Parkinson’s patients, where it can convert levodopa to dopamine. Parkinson’s is characterized by a loss of dopamine and neuronal degeneration with a concomitant loss of the AADC enzyme required to synthesize dopamine in the brain. That leads to associated impairment in motor, neuropsychiatric, and autonomic functions. Dopamine is a chemical “messenger” that is produced in the brain and is involved in the control of movement. It is made when AADC converts the chemical levodopa to dopamine. As Parkinson’s disease progresses, there is less AADC enzyme in parts of the brain where levodopa is converted to dopamine. NBIb-1817 is administered into the brain using intraoperative monitoring with magnetic resonance imaging (MRI)-facilitated targeted delivery.
