Improved Motor Function in Children with AADC Deficiency Treated with Eladocagene Exuparvovec (PTC-AADC): Interim Findings from a Phase 2 Trial

Background/Purpose: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder caused by mutations in the DDC gene, resulting in neurotransmitter deficiencies, missed motor milestones and subsequent movement disorders. Gene therapy has the potential to restore AADC and improve motor function. We report interim findings from a phase 2 study evaluating eladocagene exuparvovec (PTC-AADC).

Methods: This is an interim analysis of eight participants in a prospective, open-label trial. Children with AADC deficiency underwent bilateral intraputaminal injection of PTC-AADC. Primary endpoint was the proportion of patients achieving key milestones at 1 year (PDMS-2). Secondary endpoints included changes in PDMS-2, AIMS, Bayley-III scores, body weight, and neurologic examinations. Safety endpoints included treatment-emergent adverse events (TEAEs) and viral shedding.

Results: Patients received doses of 1.8 × 10¹¹ vg (n = 3; mean age, 55.0 months) or 2.4 × 10¹¹ vg (n = 5; mean age, 24.8 months) for ≥3 and <3 years, respectively. Increases from baseline in PDMS-2, AIMS, and Bayley-III total scores at 1 year were statistically significant. Mean body weight increased. Hypotonia, oculogyric crises, and limb dystonia decreased. No viral shedding was detected. Patients experienced ≥1 TEAE, mostly mild and not considered treatment related. Patients experienced a total of 21 serious AEs, all resolved and were unlikely to be treatment related.

Conclusion: Children with AADC deficiency achieved meaningful gains in motor function 1 year after PTC-AADC administration. No new safety signals were identified at either dose. The findings support efficacy safety of PTC-AADC in AADC deficiency and suggest benefit of early treatment.

Publication History

Article published online:
28 October 2021