FDA Approves First Gene Therapy for AADC Deficiency
Paula Cannon, PhD - November 14, 2024
FDA approved Kebilidi (eladocagene exuparvovec), the first approved gene therapy in the U.S. to be directly administered into the brain.
The FDA approved Kebilidi (eladocagene exuparvovec), a gene therapy for the treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. This is the first approved gene therapy in the U.S. to be directly administered into the brain.
AADC deficiency is a fatal, rare inherited disorder caused by mutations in the DDC gene that reduce activity of the AADC enzyme. This causes neurons to produce less dopamine, contributing to developmental delays, intellectual disabilities, abnormal movements, and autonomic nervous system dysfunction.
Signs of AADC deficiency typically appear in the first six months of life, and include involuntary movements, weak muscle tone, and sleep disturbances. People with AADC deficiency also have an increased risk of infection, which can lead to life-threatening complications.
Kebilidi, developed by PTC Therapeutics, is a one-time therapy indicated for patients 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of AADC deficiency with a severe phenotype. It's administered via four infusions in one surgical session into a large structure in the brain involved in motor control. The treatment is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy that delivers a functioning DDC gene directly into the brain to increase levels of the AADC enzyme and restore dopamine production.
The safety and effectiveness of Kebilidi were demonstrated in an open-label, single-arm clinical study in 13 pediatric patients with confirmed diagnosis of AADC deficiency. At the beginning of the study, all patients had no gross motor function and decreased AADC activity in the plasma. Twelve of the 13 patients completed motor milestone assessments at week 48 after receiving the treatment and the efficacy of Kebilidi was demonstrated based on the gross motor function improvement in eight of the 12 patients.
This approval represents an exciting development for children affected by this devastating disease. Congratulations to everyone who worked to bring this gene therapy to those children and their families.
Paula Cannon, PhD, is the president of ASGCT (2024-25) and a Distinguished Professor of Molecular Microbiology & Immunology at USC's Keck School of Medicine.
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