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|Voyager Therapeutics Announces Updates from Phase 1b Trial of VY-AADC01 for Advanced Parkinson’s Disease|
Cohort 3 Enrollment Complete with Increased Coverage of the Putamen Observed
Cohort 3 On Track for Six-Month Data Update Mid-2017
“The clinical trial of VY-AADC01 is progressing well with all five patients in Cohort 3 successfully completing treatment,” said
Increased Coverage of the Putamen Observed in Cohort 3; Six-Month Efficacy Results Expected Mid-2017
The five patients enrolled in Cohort 3 received similar infusion volumes of VY-AADC01 compared to Cohort 2 (up to 900 µL per putamen), but three-fold higher vector genome concentrations, representing up to a three-fold higher total dose of up to 4.5×1012 vector genomes (vg) of VY-AADC01 compared to patients in Cohort 2 (1.5 × 1012 vg). Patients enrolled in Cohort 3 were similar in baseline characteristics to Cohort 1 and 2. The use of real-time, intra-operative MRI-guided delivery allowed the surgical teams to visualize the delivery of VY-AADC01 and continue to achieve greater average coverage of the putamen in Cohort 3 (42%) compared to Cohort 2 (34%) with similar infusion volumes and Cohort 1 (21%) with a lower infusion volume (Figure 1). The surgical procedure was successfully completed in all five patients. Infusions of VY-AADC01 have been well-tolerated with no vector-related serious adverse events (SAEs) or surgical complications in Cohort 3, and all five patients were discharged from the hospital within two days following surgery. The Phase 1b trial remains on track to deliver six-month safety, motor function, and biomarker data from Cohort 3, as well as longer-term safety and motor function data from Cohorts 1 and 2, in mid-2017.
Figure 1: Coverage of the Putamen with VY-AADC01 is available at
Correlation Data from Cohorts 1 and 2
Interim positive results from the Phase 1b trial from Cohorts 1 and 2 reported in early
Figure 2. Interim Phase 1b Results Strengthen Clinical Hypothesis
1) Data at 6-months from baseline
“In Cohorts 1 and 2 the increased coverage of the putamen with VY-AADC01 correlated nicely with increased AADC activity and this was associated with both dose-dependent and time-dependent improvements in multiple clinical measures of motor function in patients with advanced Parkinson's disease," added
About the Phase 1b Trial of VY-AADC01 for Advanced Parkinson’s Disease
In advanced Parkinson’s disease, the putamen is depleted of dopamine and of the AADC enzyme that is responsible for converting levodopa to dopamine. VY-AADC01 is Voyager’s gene therapy vector that contains the gene that encodes the AADC enzyme. The Phase 1b, open-label trial includes up to 20 patients with advanced Parkinson’s disease and disabling motor fluctuations, treated with a single administration of VY-AADC01. The primary objective of the trial is to assess the safety and surgical coverage of ascending doses of VY-AADC01 in the putamen, a region of the brain associated with impaired motor function in Parkinson’s disease. The secondary objectives of the trial include the assessment of AADC expression and activity in the putamen measured by F-Dopa PET. In addition, changes in motor responses to levodopa are measured by a controlled intravenous infusion of levodopa and by measuring daily requirements for levodopa and related medications. Other secondary objectives include assessment of motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) and a patient-completed (Hauser) diary.
About Parkinson’s Disease and VY-AADC01
Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disease that affects approximately 700,000 people in the U.S.1 and seven to 10 million people worldwide2. It is estimated that up to 15% of the prevalent population with Parkinson’s disease, or approximately 100,000 patients in the U.S., have motor fluctuations that are refractory, or not well-controlled, with levodopa. While the underlying cause of Parkinson's disease in most patients is unknown, the motor symptoms of the disease arise from a loss of neurons in the midbrain that produce the neurotransmitter dopamine. Declining levels of dopamine in this particular region of the brain leads to the motor symptoms associated with Parkinson’s disease including tremors, slow movement or loss of movement, rigidity, and postural instability. Motor symptoms during the advanced stages of the disease include falling, gait freezing, and difficulty with speech and swallowing, with patients often requiring the daily assistance of a caregiver.
There are currently no therapies that effectively slow or reverse the progression of Parkinson’s disease. Levodopa remains the standard of care treatment, with its beneficial effects on symptom control having been discovered over 40 years ago3. Patients are generally well-controlled with oral levodopa in the early stages of the disease, but become less responsive to treatment as the disease progresses. Patients experience longer periods of reduced mobility and stiffness termed off-time, or the time when medication is no longer providing benefit, and shorter periods of on-time when their medication is effective.
The progressive motor symptoms of Parkinson’s disease are largely due to the death of dopamine neurons in the substantia nigra, a part of the midbrain that converts levodopa to dopamine, in a single step catalyzed by the enzyme AADC. Neurons in the substantia nigra release dopamine into the putamen where the receptors for dopamine reside. In advanced Parkinson’s disease, neurons in the substantia nigra degenerate and the enzyme AADC is markedly reduced in the putamen, which limits the brain’s ability to convert oral levodopa to dopamine4. The intrinsic neurons in the putamen, however, do not degenerate in Parkinson’s disease5,6. VY-AADC01, comprised of the adeno-associated virus-2 capsid and a cytomegalovirus promoter to drive AADC transgene expression, is designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located, bypassing the substantia nigra neurons and enabling the neurons of the putamen to express the AADC enzyme to convert levodopa into dopamine. The approach with VY-AADC01, therefore, has the potential to durably enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements in motor symptoms following a single administration.
1 Willis et al, Neuroepidemiology.2010;34:143–151
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