RESTORE-1 Study of Gene Therapy VY-AADC Suspends Patient Screening Due to COVID-19 Pandemic

The Phase 2 RESTORE-1 trial testing the investigational gene therapy VY-AADC has suspended the screening and enrollment of new Parkinson’s disease patients to evaluate the impact of the COVID-19 pandemic on the study’s protocols and on the safety of participants, Voyager Therapeutics has announced.

Patient enrollment and screening will resume once it’s deemed safe to do so. The company is continuing its preparations to initiate the RESTORE-2 Phase 3 study, scheduled to begin in the second half of 2020.

Parkinson’s is characterized by the death of dopamine-producing neurons, resulting in lower dopamine levels and affecting how muscle movement and coordination are regulated.

In addition, as the disease progresses, patients are thought to produce less of L-amino acid decarboxylase (AADC), an enzyme that mediates the conversion of levodopa into dopamine. This loss of AADC would make a dose of levodopa, one of the main therapies for Parkinson’s symptoms, less effective.

VY-AADC — being developed by Neurocrine Biosciences and Voyager Therapeutics — is a gene therapy made of a modified and harmless adeno-associated virus that delivers the AADC gene, which contains the instructions to produce the AADC enzyme, directly into the putamen, a large brain structure that contains dopamine receptors and is involved in movement control.

By providing AADC to putamen brain cells, VY-AADC is thought to promote levodopa’s conversion into dopamine, increasing its levels directly where it is needed and potentially easing disease symptoms.

The RESTORE-1 (NCT03562494) study plans to enroll up to 42 Parkinson’s patients who have been diagnosed for at least four years and failed to respond properly to oral medications.

Additionally, patients are required to have at least three hours of daily “off” periods — characterized by the return of motor and non-motor symptoms when levodopa’s effects wear off — as assessed by a self-reported patient diary.

Participants are randomized to either one-time administration of VY-AADC or a placebo surgery.

The trial’s main (primary) efficacy goal is to assess “on” times without troublesome dyskinesia (involuntary, jerky movements), or good “on” times, as measured by a self-reported patient diary at 12 months. Follow-up will continue beyond the 12 months to collect further safety data and to assess how long the therapy’s potential benefits last.

Additional (secondary) goals include assessing changes in response to levodopa and also in activities of daily living with the United Parkinson’s Disease Rating Scale, quality of life with the Parkinson’s Disease Questionnaire, and global function through the proportion of patients with improved Clinical Global Impression scores.

The therapy’s safety as well as changes in AADC enzyme activity will also be evaluated.

The U.S. Food and Drug Administration granted regenerative medicine advanced therapy designation to VY-AADC in June 2018 for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.