FDA Approves Kebilidi, First Gene Therapy Directly Administered to the Brain, for AADC Deficiency

Key Insights

• The FDA has granted accelerated approval to Kebilidi (eladocagene exuparvovec-tneq) for treating AADC deficiency in both children and adults, addressing the full spectrum of disease severity.
• Kebilidi is the first gene therapy approved in the U.S. that is directly administered to the brain, offering a novel approach to treating this rare neurological disorder.
• This gene replacement therapy restores dopamine synthesis in the brain by delivering it directly to the putamen, improving motor development in patients with AADC deficiency.

The FDA has granted accelerated approval to Kebilidi (eladocagene exuparvovec-tneq) for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency in children and adults. This marks the first gene therapy to be directly administered to the brain to receive FDA approval.

AADC deficiency is a rare genetic disorder caused by mutations in the DDC gene, which encodes the AADC enzyme. This enzyme is crucial for the production of neurotransmitters like dopamine and serotonin. Deficiency leads to impaired motor function, developmental delays, and autonomic nervous system dysfunction.

Mechanism of Action

Kebilidi functions as a gene replacement therapy. It is administered directly into the putamen, a region in the brain, via a minimally invasive neurosurgical procedure. The therapy delivers a functional copy of the DDC gene, restoring dopamine synthesis in the brain and improving motor development.

Clinical Evidence

The FDA's approval is based on data from an ongoing clinical trial. This trial aims to provide confirmatory evidence regarding the long-term effects of Kebilidi. The therapy has already been approved in the European Union in 2022 and in the United Kingdom in 2023, where it is marketed as Upstaza.

Company Insights

PTC Therapeutics, a biopharmaceutical company headquartered in Mountain View, California, is responsible for bringing Kebilidi to market in the US. PTC Therapeutics acquired Agilis Biotherapeutics, the original developer of Kebilidi, in August 2018. According to Matthew B. Klein, CEO of PTC Therapeutics, this approval represents a pioneering approach to treating highly morbid neurologic diseases, and he expressed pride in his team's commitment to achieving this regulatory milestone.