FDA Grants Accelerated Approval to Gene Therapy for the Treatment of AADC Deficiency

Kebilidi (eladocagene exuparvovec-tneq; PTC Therapeutics, Warren, NJ) has been granted Food and Drug Administration (FDA) approval under the Accelerated Approval pathway for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. Kebilidi is an adeno-associated virus vector-based gene therapy administered by intraputaminal infusion. It is the first gene therapy to receive FDA approval for the treatment of this genetic disorder.

The FDA’s decision was based on findings from an ongoing global clinical trial demonstrating safety and efficacy of Kebilidi as a treatment for AADC deficiency. The open-label, single-arm clinical study includes 13 pediatric participants with confirmed diagnosis of AADC deficiency with no gross motor function and decreased AADC activity in plasma. No gross motor function comprises the most severe presentation of AADC deficiency. All participants received treatment with Kebilidi with outcomes compared with a natural history cohort.

• 12 of the 13 participants completed motor milestone assessments at week 48 after receiving treatment.
• 8 of 12 treated participants showed gross motor function improvement, which has not been reported in untreated patients, demonstrating the efficacy of Kebilidi treatment.
• The most common adverse reactions are dyskinesia, fever, low blood pressure, anemia, increased saliva production, insomnia, procedural complications (eg, respiratory and cardiac arrest), and low levels of potassium, phosphate, and/or magnesium.
• Confirmatory evidence will be provided after long-term follow-up of study participants.

"I am proud of our team's unwavering commitment to achieve this important regulatory milestone,” said Matthew B. Klein, MD, CEO of PTC Therapeutics. “We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."

AADC deficiency is a rare genetic disorder associated with mutations in the DDC gene that encodes the aromatic L-amino acid decarboxylase enzyme. People present symptoms within the first few months of life, including hypotonia, developmental delay, dystonia and dyskinesia, gastrointestinal dysmotility, autonomic symptoms, and oculogyric crises. Children with this disorder are at high risk of death within the first 10 years of life.

The FDA authorized the use of the SmartFlow Neuro Cannula (Clearpoint Neuro, Solana Beach, CA) for use in administering Kebilidi.