Voyager Therapeutics, Inc. Announces FDA Clearance of Investigational New Drug Application for VY-AADC for Advanced Parkinson’s Disease
January 23, 2018 at 05:34 pm IST
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Voyager Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for VY-AADC, allowing the Company to formally initiate clinical trial sites, screen and begin dosing patients for its pivotal Phase 2-3 program for advanced Parkinson’s disease. As part of this IND, the chemistry, manufacturing, and controls section included data demonstrating comparability between VY-AADC produced under good manufacturing practice (GMP) using Voyager’s baculovirus/Sf9 manufacturing process and VY-AADC produced using a mammalian cell system consisting of triple-transfection of human embryonic kidney (HEK293) cells. Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disease that affects approximately one million people in the U.S. and seven to 10 million people worldwide1. 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 region of the brain, the putamen, 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 ago2. 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 dopamine3. The intrinsic neurons in the putamen, however, do not degenerate in Parkinson’s disease4,5. VY-AADC, 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-AADC, therefore, has the potential to durably enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.
Voyager Therapeutics, Inc. is a biotechnology company focused on advancing neurogenetic medicines. The Companyâs pipeline includes programs for Alzheimerâs disease, amyotrophic lateral sclerosis (ALS), Parkinsonâs disease, and multiple other diseases of the central nervous system. Many of its programs are derived from its TRACER AAV capsid discovery platform, which is used to generate novel capsids and identify associated receptors to potentially enable high brain penetration with genetic medicines following intravenous dosing. Its pipeline of programs, all of which are in preclinical development, include Anti-Tau Antibody (VY-TAU01), SOD1 Silencing Gene Therapy Program, Tau Silencing Gene Therapy Program, Vectorized Anti-Amyloid Antibody Early Research Program, Friedreichâs Ataxia Program: VY-FXN01, GBA1 Gene Replacement Program, HD Program, and others. VY-TAU01 is for the treatment of Alzheimerâs disease. SOD1 Silencing Gene Therapy Program is for the treatment of ALS.