Abstract Details

Title PD-1102: A Phase 1 study of VY-AADC01 Administered Using a Posterior Approach in Patients with Parkinson’s Disease and Motor Fluctuations

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-017

Objective Evaluate safety, putaminal coverage, aromatic L-amino acid decarboxylase (AADC) activity, and clinical outcomes at 12 months in patients with Parkinson’s disease and motor fluctuations treated with VY-AADC01, an AAV2-AADC vector-based therapy administered to bilateral putamen.

Background The phase 1 study (PD-1101) showed improved putaminal coverage, AADC activity, and clinical outcomes with dose escalation and improved administration of VY-AADC. This study (PD-1102) changed to a single administration trajectory per putamen targeting the posterior tail, with a goal of increasing coverage and improving clinical outcomes.

Design/Methods

Eight subjects with similar baseline characteristics to those in PD-1101 were administered up to 2.6×10¹² vg/mL in up to 1.8 mL per putamen (total dose up to 9.4×10¹² vg) using a single parietal-occipital trajectory per putamen, optimizing vector delivery to motor areas in postcommisural putamen. VY-AADC01 was admixed with gadoteridol, allowing real-time MR imaging of the location and volume of infusate; AADC activity was assessed by (18)F-DOPA PET at baseline and <7 months. Clinical measures included change in antiparkinsonian medications, subject-reported diary ON and OFF times, and UPDRS.

Results At baseline, mean age was 56.8 years and mean PD duration 9.2 years; subjects reported a mean 6.8 hours of diary OFF time and 9.1 hours of diary ON time. There were no vector-related serious adverse events; two subjects experienced mild surgical intra-cerebral hemorrhage, which resolved without residual deficits. Mean VY-AADC01 coverage of the putamen was 53.5%. AADC activity by (18)F-DOPA PET increased to levels similar to healthy adults (Feigin, 2002) and there was a 33% reduction in the need for antiparkinsonian medications. Diary ON and OFF times, and UPDRS at 12 months will be reported.

Conclusions Modifying the neurosurgical administration of VY-AADC01 resulted in increased putaminal coverage and associated AADC activity. Together with the reductions in antiparkinsonian medications, these findings suggest potential clinical benefit.

Authors/Disclosures
Amber D. Van Laar, MD (Asklepios BioPharmaceutical Inc) PRESENTER	Dr. Van Laar has received personal compensation for serving as an employee of Asklepios Biopharmaceutical. The institution of an immediate family member of Dr. Van Laar has received research support from Asklepios BioPharmaceutical Inc.
	No disclosure on file
Chadwick W. Christine, MD, FAAN	The institution of Dr. Christine has received research support from Michael J Fox Foundation for Parkinson's Research. The institution of Dr. Christine has received research support from Aspen Neurosciences. The institution of Dr. Christine has received research support from ASK BIo. The institution of Dr. Christine has received research support from Bayer.
Stewart A. Factor, DO, FAAN (Emory University School of Medicine)	Dr. Factor has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine. Dr. Factor has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Factor has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. The institution of Dr. Factor has received research support from Biohaven. The institution of Dr. Factor has received research support from Neurocrine. The institution of Dr. Factor has received research support from Supernus. The institution of Dr. Factor has received research support from Sun Pharmaceuticals Advanced Research Company. The institution of Dr. Factor has received research support from Aspen. The institution of Dr. Factor has received research support from RHO. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care.
Robert Gross	No disclosure on file
Sandra K. Kostyk, MD, PhD (Prilenia Therapeutics.)	Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WaveLifeScience. Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Kostyk has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prilenia Therapeutics. The institution of Dr. Kostyk has received research support from Michael J Fox Foundation. The institution of Dr. Kostyk has received research support from Craig Nielsen Foundation. The institution of Dr. Kostyk has received research support from CHDI Foundaton. The institution of Dr. Kostyk has received research support from UniQure. The institution of Dr. Kostyk has received research support from Voyager Therapeutics. The institution of Dr. Kostyk has received research support from WaveLife Sciences. The institution of Dr. Kostyk has received research support from Vaccinex . The institution of Dr. Kostyk has received research support from Neurocrine Biosciences. The institution of Dr. Kostyk has received research support from Prilenia.
	No disclosure on file
Marc de Somer, MD (Prilenia)	No disclosure on file
	No disclosure on file
Bernard M. Ravina, MD, MSCE (Voyager Therapeutics, Inc.)	Dr. Ravina has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Ravina has stock in Praxis.
Adrian Kells	No disclosure on file
Krzysztoffs Bankiewicz, MD	No disclosure on file
Paul Larson	No disclosure on file

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