FDA Approves PTC Therapeutics' KEBILIDI, a Gene Therapy for AADC Deficiency

• The FDA has granted accelerated approval to KEBILIDI (eladocagene exuparvovec-tneq), a gene therapy for AADC deficiency, marking the first FDA-approved gene therapy directly administered to the brain.
• KEBILIDI is indicated for both children and adults with AADC deficiency, addressing the full spectrum of disease severity and offering a new treatment option for this rare genetic disorder.
• The approval is based on clinical trial data demonstrating improved motor development milestones following gene therapy, with continued approval contingent on confirmatory evidence from long-term follow-up studies.
• PTC Therapeutics received a Rare Disease Priority Review Voucher, which it plans to monetize, alongside the BLA approval, further supporting its commitment to developing treatments for rare disorders.

PTC Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to KEBILIDI™ (eladocagene exuparvovec-tneq) for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency in both children and adults. This marks the first gene therapy approved in the United States that is directly administered to the brain.

KEBILIDI is a gene replacement therapy delivered directly to the putamen of the brain via a stereotactic neurosurgical procedure. It is designed to address the underlying genetic defect in AADC deficiency by delivering a functional DDC gene, thereby increasing AADC enzyme production and restoring dopamine synthesis.

Clinical Efficacy and Safety

The FDA's accelerated approval is based on safety and efficacy data from an ongoing global clinical trial (PTC-AADC-GT-002). Results from the trial demonstrated that gene therapy led to de novo synthesis of dopamine and progressive acquisition of motor development milestones. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

The most common adverse reactions (≥15%) observed in patients treated with KEBILIDI were dyskinesia (77%), pyrexia (38%), hypotension (31%), anemia (31%), salivary hypersecretion (23%), hypokalemia (23%), hypophosphatemia (23%), insomnia (23%), hypomagnesemia (15%), and procedural complications, including respiratory and cardiac arrest (15%).

AADC Deficiency: A Devastating Genetic Disorder

AADC deficiency is a rare, life-threatening genetic disorder that impairs the synthesis of dopamine and serotonin, neurotransmitters crucial for motor function, behavior, and autonomic functions. Children with AADC deficiency often experience severe disability, including movement disorders, developmental delays, and autonomic dysfunction. Oculogyric crises, characterized by involuntary, sustained upward gaze, are also common and distressing.

Dosing and Administration

KEBILIDI is administered via a stereotactic surgical procedure, a minimally invasive neurosurgical technique. The procedure is performed by qualified neurosurgeons at specialized centers. The therapy is delivered directly into the putamen using the SmartFlow Neuro Cannula.

Regulatory and Commercialization Plans

Along with the BLA approval, PTC Therapeutics was granted a Rare Disease Priority Review Voucher, which the company intends to monetize. Launch preparations are underway, with centers of excellence identified and surgeons trained in the administration procedure.

Contraindications and Warnings

KEBILIDI is contraindicated in patients who have not achieved skull maturity, as assessed by neuroimaging. Warnings and precautions include potential procedure-related complications such as respiratory and cardiac arrest, CSF leak, intracranial bleeding, neuroinflammation, acute infarction, and infection. Patients should be monitored for dyskinesia, which has been reported after KEBILIDI administration.