The FDA has granted approval to eladocagene exuparvovec-tneq (Kebilidi; PTC Therapeutics Inc) for the treatment of both adult and pediatric patients suffering from aromatic L-amino acid decarboxylase (AADC) deficiency. This marks the first FDA-approved gene therapy for this rare genetic disorder.
AADC deficiency is characterized by a reduction in the activity of the aromatic l-amino acid decarboxylase enzyme, crucial for neurotransmitter synthesis. Symptoms, which typically manifest in the first months of life, include abnormal eye movement, movement disorders, autonomic dysfunction, and mood disturbances. Brain MRIs often show normal or non-specific abnormalities.
Clinical Trial Data
The approval was based on data from an open-label, single-arm clinical trial involving 13 pediatric patients with AADC deficiency. All participants exhibited no gross motor functions and decreased AADC activity at the study's outset. The trial compared eladocagene exuparvovec-tneq against no treatment, with motor assessments conducted on 12 of the 13 patients at week 48. Results indicated that 8 of the 12 treated individuals demonstrated improved gross motor function compared to the untreated group, according to the FDA.
Nicole Verdun, MD, director of the Office of Therapeutic Products in the Center for Biologics Evaluation and Research at the FDA, stated, "AADC deficiency can cause a range of debilitating symptoms, including life-threatening complications. Today’s approval represents important progress in the advancement and availability of safe and effective treatments for debilitating genetic disorders."
Administration and Mechanism of Action
Eladocagene exuparvovec-tneq is administered as 4 infusions in a single surgical session into the brain area responsible for motor control. This procedure is performed at specialized medical centers equipped for pediatric stereotactic neurosurgery. Post-infusion, the expression of AADC increases dopamine production, which is vital for movement, attention, learning, and memory.
The clinical trial includes an extension and long-term extension phase to evaluate clinical information, changes in motor development, AADC-specific symptoms, pharmacodynamic measures, long-term safety, and efficacy data.
Adverse Events
The most common adverse events observed in the clinical trial included dyskinesia, fever, low blood pressure, anemia, increased saliva production, insomnia, and low levels of potassium, phosphate, and magnesium, as well as procedural complications.
