Abstract Details

Title Eladocagene Exuparvovec Gene Therapy Improves Motor Development in Patients With Aromatic L-Amino Acid Decarboxylase Deficiency

Topic Child Neurology and Developmental Neurology

Presentation(s) S39 - Child Neurology and Developmental Neurology (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background AADC deficiency is caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity; it is characterized by motor impairments and inability to attain developmental milestones. Eladocagene exuparvovec (PTC-AADC) is a recombinant adeno-associated viral vector serotype 2 carrying the coding sequence for human AADC.

Objective To assess the effects of gene therapy with eladocagene exuparvovec ion the development of motor skills in patients with aromatic l-amino acid decarboxylase (AADC) deficiency.

Design/Methods

PTC-AADC was infused bilaterally in the putamena of 28 children with AADC deficiency in 3 clinical trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients at 26 February 2020 cutoff, ongoing]). Patients received a total of 1.8 × 10¹¹ vg (n=21) or 2.4 × 10¹¹ vg (n=7; AADC-011)] and were assessed for the motor milestone attainment using the Peabody Developmental Motor Scale, 2nd edition (PDMS-2) and Alberta Infant Motor Scale (AIMS). PDMS-2 contains subscales for interrelated motor abilities and AIMS contains subscales for elements of movement in different positions

Results All patients treated with PTC-AADC had clinically meaningful increases in total PDMS-2 and total AIMS scores, which were maintained or improved over time, up to 60 months (LS mean change from baseline [SE] 15.0 [8.54] and 27.5 [2.62] respectively, at 60 months, the last measured timepoint). Similar increases were noted for PDMS-2 and AIMS subscores. Clinically meaningful increases from baseline in PDMS-2 total scores were seen as early as 3 months post-treatment and extended to at least 60 months.

Conclusions

The data indicate that PTC-AADC can provide a durable, positive impact on motor development in patients with AADC deficiency.

Authors/Disclosures
Paul Wuh-Liang Hwu PRESENTER	Paul Wuh-Liang Hwu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics Inc.. Paul Wuh-Liang Hwu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics. The institution of Paul Wuh-Liang Hwu has received research support from PTC therapeutics.
Yin-Hsiu Chien	Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis/Norvatis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Yin-Hsiu Chien has received research support from Sanofi Genzyme.
	No disclosure on file
	No disclosure on file
Antonia Wang (PTC Therapeutics, Inc.)	No disclosure on file
Traci B. Schilling, MD	No disclosure on file
	No disclosure on file