FDA approves first-ever gene therapy to be directly administered to the brain
The FDA has granted accelerated approval to Kebilidi (eladocagene exuparvovec-tneq) as a treatment for children and adults with AADC deficiency, including the full spectrum of disease severity. This approval makes Kebilidi the first therapy that is directly administered to the brain to ever gain approval in the US.
AADC deficiency is caused by mutations of the gene that encodes for the aromatic L-amino acid decarboxylase (AADC) enzyme, which plays an important role in the nervous system. The ADDC enzyme can be found in neurons, where it is involved in the production of the neurotransmitters dopamine and serotonin. Changes in the levels of these neurotransmitters can affect normal development, causing intellectual disabilities, movement impairment and dysfunction of the autonomic nervous system.
Kebilidi is intended as a gene replacement therapy that is directly administered to the putamen, a structure located in the center of the brain, through a minimally invasive neurosurgical procedure. Following the administration of Kebilidi, the synthesis of dopamine is restored in the brain, which leads to an improvement in motor development in patients.
The approval of Kebilidi is based on data from an ongoing clinical trial, which will provide confirmatory evidence on the long-term effects of the treatment. The therapy was previously approved in the EU in 2022 and in the UK in 2023 under the name Upstaza.
PTC Therapeutics is a global biopharmaceutical company with headquarters in Mountain View, California. The company currently has six treatments on the market that target rare diseases in the areas of neurology and metabolism, such as Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), hereditary transthyretin amyloidosis (hATTR), and familial chylomicronemia syndrome (FCS).
Kebilidi was originally developed by Agilis Biotherapeutics, a gene therapy company based in New Jersey. In August 2018, PTC Therapeutics acquired Agilis, gaining ownership of multiple gene therapy programs including an AADC therapy that eventually became Kebilidi/Upstaza.
"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," said Matthew B. Klein, Chief Executive Officer of PTC Therapeutics. "I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."
