PTC Therapeutics, Inc. (NASDAQ: PTCT) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for KEBILIDI™ (eladocagene exuparvovec-tneq), a gene therapy indicated for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency in adult and pediatric patients. This marks the first gene therapy approved in the United States that is directly administered to the brain.
Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics, stated, "PTC has once again pioneered a new approach to treating highly morbid neurologic diseases. 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."
KEBILIDI™, a recombinant adeno-associated virus serotype 2 (rAAV2)-based gene therapy, contains the human DDC gene. It is designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production. The therapy is administered through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure.
Clinical Efficacy and Safety
The FDA's accelerated approval was based on safety and clinical efficacy findings from the ongoing global clinical trial (PTC-AADC-GT-002). The efficacy was demonstrated by the change from baseline in gross motor milestone achievement at 48 weeks post-treatment. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
The most common adverse reactions (≥15%) 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 genetic disorder that results in the inability to synthesize dopamine, a neurotransmitter essential for motor function. This deficiency leads to severe disability and suffering from the first months of life, affecting physical, mental, and behavioral aspects. Children with AADC deficiency may experience oculogyric crises, which are distressing, painful episodes resembling seizures.
Without effective treatment, the lives of affected children are severely impacted and shortened. Ongoing physical, occupational, and speech therapy, along with interventions including surgery, are often required to manage potentially life-threatening complications such as infections and severe feeding and breathing problems.
Important Safety Information
KEBILIDI™ is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging, as skull maturity is needed for stereotactic neurosurgical administration. Procedural complications, including respiratory and cardiac arrest, have been reported after neurosurgery required for KEBILIDI™ administration. Patients should be monitored for procedure-related adverse events, including cerebrospinal fluid (CSF) leak, intracranial bleeding, neuroinflammation, acute infarction, and infection.
Dyskinesia was reported after administration of KEBILIDI™, with events occurring within 3 months of administration and some requiring hospitalization. Monitoring for signs and symptoms of dyskinesia is recommended, and dopamine antagonists may be considered to control symptoms.
Future Plans
PTC Therapeutics plans to monetize the Rare Disease Priority Review Voucher granted along with the Biologics License Application approval. Launch preparations are underway, with centers of excellence already identified and surgeons trained in the procedure to deliver the gene therapy.
