Voyager Reports Positive Interim Data from Phase 1b Trial of Gene Therapy for Advanced Parkinson’s Disease

Ana de Barros, PhD avatar

by Ana de Barros, PhD |

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gene therapy VY-AADC01

Voyager Therapeutics has reported positive interim six- and 12-month data from its ongoing Phase 1b clinical trial, showing that its gene therapy VY-AADC01 was well-tolerated and resulted in clinically relevant outcomes for patients with advanced Parkinson’s disease (PD).

The Phase 1b open-label clinical trial (NCT01973543), which is currently recruiting participants, is evaluating the safety and efficiency of VY-AADC01 administered by magnetic resonance imaging-guided delivery into the putamen, a brain structure involved in the regulation of movements, in patients with advanced PD who have fluctuating responses to levodopa. Patients enrolled in cohort 1 received up to of 7.5 × 1011 vector genomes (vg) of  VY-AADC01 (single infusion), and patients in cohort 2 received up to  1.5 × 1012 vg.

The primary endpoint is VY-AADC01’s safety at ascending dose levels. Secondary endpoints include an evaluation of the surgical coverage of the putamen and the assessment of the effect of the therapy on the AADC enzyme expression and activity in the putamen before and after treatment, as measured by positron emission tomography (PET).

The interim results are from 10 patients with PD treated in cohorts 1 and 2 at six months (five patients in each cohort), and data from five patients in cohort 1 and three patients in cohort 2 who have reached 12 months of follow-up.

Both cohorts showed that accurate MRI-guided delivery VY-AADC01 at escalating doses was well tolerated. The gene therapy delivery increased coverage of the putamen, the activity of the enzyme AADC and enhanced patients’ response to levodopa. In addition, the data showed that the gene therapy resulted in motor function improvements.

These results were more pronounced in patients assigned to a higher dose in cohort 2, with improved off-medication and on-medication scores as measured by the Parkinson disease rating scale (UPDRS), and corresponding improvements in patients’ diary hours, indicating that the treatment prolonged the effect of levodopa.

“At 12 months in Cohort 2, treatment with VY-AADC01 resulted in a 14-point, or 44%, improvement in UPDRS-III off medication, a 9-point, or 55% improvement in UPDRS-III on medication, and a 2.2 hour, or 48%, decrease in diary off-time from baseline,” said Bernard Ravina, MD, vice president of clinical development at Voyager Therapeutics, in a press release.

“Very importantly, these improvements in motor function occurred with a substantial 34% reduction in daily doses of oral levodopa and related medications at six months in cohort 2 that was maintained at 12 months, a magnitude that we find compelling and consistent with the mechanism of action of VY-AADC01. The dose-escalating portion of this trial continues and we plan to complete cohort 3 enrollment in early 2017, report 6-month data from this cohort, as well as longer-term data from cohorts 1 and 2 in mid-2017, and present results from this trial at a medical conference in the first half of next year”, he added.

Patients with PD are normally treated with levodopa to compensate the dopamine loss that the disease causes. Levodopa is converted to dopamine by the enzyme Aromatic L-Amino Acid Decarboxylase (AADC). As the disease progresses, levodopa therapy becomes less effective and is associated with motor fluctuations, involuntary movements and other complications.

VY-AADC01 comprises the adeno-associated virus-2 capsid and a cytomegalovirus promotor to drive AADC transgene expression. The gene therapy is designed to deliver the AADC gene directly into the putamen where the dopamine receptors are located. By increasing production of AADC, VY-AADC01 aims to prolong the efficacy of levodopa.

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