Voyager Therapeutic's Parkinson's Trial Shows Positive Results
VY-AADC is Voyager’s gene therapy vector. Parkinson’s disease is a neurogenerative disorder that primarily affects dopamine-producing brain cells in the area of the brain called substantia nigra. Slow to develop, the most common symptoms are tremors, slow movements, rigid limbs, and gait and balance problems. In advanced Parkinson’s the putamen’s dopamine levels are depleted as is the enzyme aromatic L-amino acid decarboxylase (AADC). AADC converts levodopa to dopamine. VY-AADC has the potential to provide improved motor function and cut patients’ need for oral levodopa and other dopaminergic medications.
The updated data indicates the therapy is continuing to show durable, dose-dependent and time-dependent improvements in the patients’ motor function after a one-time treatment. The measures used to monitor the patients’ motor function include patient-reported diaries, Parkinson’s disease rating scales, quality of life, and evaluation of on-time without troublesome dyskinesia at 12 months. The updated results also include a durable 2.1-hour improvement in patient-reported diary on-time without troublesome dyskinesia from baseline to three years, as well as 3.5-hour improvement from baseline to 18 months, and from baseline to six months of 1.5 hours that plateaued from six to 12 months.
“Off-times” are the motor fluctuations noted when the patient’s medication isn’t working optimally and Parkinson’s symptoms return. “On-times” are when it is working optimally.
“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, Voyager’s chief medical officer, in a statement. “In our dose-ranging Phase Ib trial, we systematically increase the dose of VY-AADC to select an optimal dose prior to initiating our pivotal program. We believe we have achieved this with our Cohort 2 dose, in which patients increase their on-time without any dyskinesia by five hours at 19 months and reduce their off-time by more than 60 percent.”
Ravina went on to say, “Not unexpectedly, our Cohort 3 dose resulted in greater rates of levodopa-induced dyskinesia that resolved with marked reductions in patients’ oral levodopa and related medicines but resulted in less robust control of motor function compared to Cohort 2 by 12 months. Given the improvements in motor function and wider spectrum to titrate oral levodopa with our Cohort 2 dose, are excited to consider this as our likely dose in the pivotal program while still planning to review the six-months results from the Phase I posterior trajectory trial next quarter.”
The company expects to review the Phase Ib data with the U.S. Food and Drug Administration (FDA) as part of a Type C meeting, and plans to dose the first patient in the pivotal Phase II-III program in mid-2018.
In September 2017, shortly after Voyager reported early-stage proof-of-concept data on VY-AADC01, John Carroll with Endpoints News, wrote, “The gene therapy is designed to complete a simple task. Parkinson’s patients typically respond well to levodopa to provide the dopamine patients need following the death of neurons in the brain. But their response declines, requiring ever higher doses of levodopa with ever diminishing returns. Voyager’s gene therapy introduces an enzyme that converts levodopa to dopamine, and this study underscores that patients were able to get a better effect with lower dosing—a major accomplishment.”
And today’s update seems to support that even more.