VY-AADC Gene Therapy Receives FDA RMAT Designation for Parkinson


Across 3 cohorts, the therapy showed improvements in on-time without troublesome dyskinesia, ranging from 2.1 hours to 3.5 hours.

Bernard Ravina, MD, MS

Voyager Therapeutics announced that the US Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to its VY-AADC gene therapy treatment for Parkinson disease (PD) in patients with motor fluctuations that are refractory to medical management.

Just months prior, in January, the FDA cleared the therapy’s Investigational New Drug Application (IND).1 The RMAT designation was granted based on the data from a phase Ib trial examining the therapy, Robert Pietrusko, PharmD, senior vice president, regulatory affairs and quality assurance, Voyager, said.2

The primary objective was to assess the safety and tolerability and to test dosages of VY-AADC administered under magnetic resonance imaging (MRI) guidance to the putamen.3

The secondary objectives include an assessment of AADC expression and activity in the putamen as measured by positron emission tomography (PET) using [18F] fluorodopa (18F-DOPA), as well as assessments of motor function and activities of daily living, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS-III and UPDRS-II, respectively), quality of life, and a patient-completed Hauser diary.

The open-label trial included 15 patients with advanced PD and disabling motor fluctuations, divvied equally into 3 cohorts, all of which were treated with a single administration of the VY-AADC gene therapy. Cohort 1 received a total dose of up to 7.5×1011 vg. Meanwhile, Cohort 2 received a total dose of up to 1.5 × 1012 vg, and Cohort 3 received up to 4.5×1012 vg.

Data showed a 2.1-hour improvement in patient-reported diary on-time without troublesome dyskinesia over the 3-year period in Cohort 1, from the baseline 10.5-hour average on-time. In Cohort 2, a clinically significant improvement from baseline of 3.5 hours was seen from baseline to 18 months, while Cohort 3 experienced a 1.5-hour improvement from baseline to 6 months that held for 12 months.

“We continue to be pleased with the duration and magnitude of effect of VY-AADC on multiple measures of patients’ motor function and quality of life, which is consistent with the mechanism of action of VY-AADC suggesting a greater capacity for patients to make more dopamine and improve their motor function with less need for oral levodopa,” said Bernard Ravina, MD, MS, chief medical officer, Voyager, in a statement.

Ravina added that at 18 months, Cohort 2 patients had a mean increase of 5.1 hours per day of on-time without any dyskinesia, with 65% less off time.

Additionally, Cohorts 2 and 3 saw quality of life improvements via mean patient-reported 39-item Parkinson’s Disease Questionnaire (PDQ-39) score reductions of -8.4 and -9.1, respectively, from baseline to 12 months. Cohort 1 experienced a 6-month score reduction of -2.9, though it fluctuated up to -1.9 at 12 months.

Patients in the trial were instructed to decrease their daily doses of oral levodopa and related medications, or levodopa equivalent doses (LED), in order to achieve optimum motor control in response to observed severe dyskinesia post-treatment with VY-AADC. The mean amount of PD medications at baseline was 1526 mg of oral LED per day. The disease LEDs were reduced by an average of 15%, 33%, and 42% each for Cohorts 1, 2, and 3, respectively, from baseline to 6 months. Cohort 3 maintained the reduction through 12 months, while Cohorts 1 and 2 saw the effect maintained over 18 months.

Safety examinations revealed the VY-AADC infusions to be generally well-tolerated across all cohorts. No vector-related serious adverse events (AEs) were reported, and 14 of 15 patients were discharged within 2 days following surgery. A single patient reported 2 serious AEs: a pulmonary embolism and heart arrthymia, though it was determined these were most likely related to immobility during administration. The patient was treated, and the AEs were resolved, and as a consequence, deep vein thrombosis prophylaxis was added to the protocol.

Voyager is planning a phase II-III pivotal program and is expecting to discuss these designs with the FDA during a Type C meeting. The program is on pace to dose its first patient mid-2018.


1. Voyager Therapeutics announces FDA regenerative medicine advanced therapy (RMAT) designation granted for VY-AADC for the treatment of Parkinson’s disease [press release]. Voyager Investor Relations and Corporate Communications. Cambridge, Massachusetts. ir.voyagertherapeutics.com/phoenix.zhtml?c=254026&p=irol-newsArticle&ID=2355428. Accessed June 21, 2018.

2. Voyager Therapeutics announces FDA clearance of investigational new drug application for VY-AADC for advanced Parkinson’s disease [press release]. Voyager Investor Relations and Corporate Communications. Cambridge, Massachusetts. ir.voyagertherapeutics.com/phoenix.zhtml?c=254026&p=irol-newsArticle&ID=2327863. Accessed June 21, 2018.

3. Voyager Therapeutics announces longer-term data from ongoing phase 1b trial of VY-AADC for advanced Parkinson’s disease [press release]. Voyager Investor Relations and Corporate Communications. Cambridge, Massachusetts. ir.voyagertherapeutics.com/phoenix.zhtml?c=254026&p=irol-newsArticle&ID=2337283. Accessed June 21, 2018.

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