Voyager Therapeutics, a Cambridge, MA-based clinical-stage company developing gene therapies for central nervous system disorders, has announced positive interim data of its ongoing Phase 1b trial of VY-AADC01 for the treatment of Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disorder caused by the loss of neurons that release dopamine in the striatum. Levodopa medication is the standard treatment prescribed to patients to compensate for the loss of dopamine. Levodopa is converted to dopamine by the enzyme Aromatic L-Amino Acid Decarboxylase (AADC). As Parkinson’s disease progresses, levodopa therapy becomes less effective and is associated with motor fluctuations, involuntary movements and other complications.
The present VY-AADC01 trial is designed to evaluate the safety of increasing AADC levels in the striatum via AADC gene delivery. The human AADC gene is inserted into an adeno-associated viral (AAV2) vector and is injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery. Subjects continue to take Parkinson’s disease medications, including levodopa.
The safety and potential clinical responses to VY-AADC01 was assessed by repeated clinical evaluations of Parkinson’s disease, cognitive tests, laboratory blood tests and neuroimaging. The trial includes four cohorts; an initial cohort received 7.5 x 1011 vector genomes of VY-AADC01and a second cohort received 1.5 x 1012 vector genomes. The third set of patients will receive 4.7x 1012 and the fourth cohort will receive the highest dose of 8.8 x 1012 vector genomes.
The interim data from cohorts 1 and 2 of the present gene therapy trial demonstrated that precise MRI-guided delivery of VY-AADC01 was well tolerated and resulted in increased AADC enzyme activity, enhanced response to levodopa, and dose-related, clinically relevant improvements in patients’ motor function. Among the five patients in cohort two, AADC activity rose by 56% and levodopa dosages fell 34% over the first six months of the study. These effects were maintained and in some patients improved at 12 months of follow-up.
Voyager will continue the dose escalation trial with cohort 3 enrollment expected to complete in early 2017. The company intends to update 6-month interim data from this cohort and long term efficacy data from cohorts 1 and 2 in mid-2017. Following the news, Voyager’s shares has increased 35% in after-hours trading.
Source: Parkinson’s gene therapy data sparks Voyager stock jump; Press Release