Abstract Details

Title Eladocagene Exuparvovec Improves Body Weight and Reduces Respiratory Infections in Patients With Aromatic L-Amino Acid Decarboxylase Deficiency

Topic Child Neurology and Developmental Neurology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-001

Background

AADC deficiency is caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity. Patients with AADC deficiency often have feeding, swallowing, and gastrointestinal problems, which may contribute to low body weight. Upper respiratory tract infections (URTIs) and pneumonia are major causes of morbidity in these patients. Eladocagene exuparvovec is a recombinant adeno-associated viral vector serotype 2 carrying the coding sequence for the human AADC gene.

Objective To assess the effects of gene therapy with eladocagene exuparvovec on body weight and rate of upper respiratory infections in patients with aromatic l-amino acid decarboxylase (AADC) deficiency.

Design/Methods Eladocagene exuparvovec was bilaterally infused into 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 Feb 2020 cutoff date, ongoing]). Patients received 1.8 × 10¹¹ vg (n=21) or 2.4 × 10¹¹ vg (n=7; AADC-011)]. Body weight was measured at baseline and at 12-month follow-up and compared with age- and gender-matched values for children without AADC deficiency. Rate of URTI/pneumonia was measured annually for 5 years after therapy.

Results

At baseline, most patients (83.3%, 20/24) had a body weight ≤3rd percentile. At 12 months, 95.9% maintained or gained weight relative to age- and gender-matched children without AADC deficiency; 42% (10/24) shifted to a higher percentile, and 54% (13/24) maintained the same percentile as at baseline. The annual rate of URTI/pneumonia decreased from 2.41 at 1 year after treatment to 0.31 at 5 years after treatment.

Conclusions

These results demonstrate the efficacy of eladocagene exuparvovec in improving body weight and reducing respiratory infections 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
Antonia Wang (PTC Therapeutics, Inc.)	No disclosure on file
Traci B. Schilling, MD	No disclosure on file
	No disclosure on file