공시 • Nov 14
PTC Therapeutics, Inc. Announces FDA Approval of AADC Deficiency Gene Therapy
PTC Therapeutics, Inc. announced the U.S. Food and Drug Administration (FDA) accelerated approval of its gene therapy for the treatment of AADC deficiency, the first-ever gene therapy approved in the United States that is directly administered to the brain. The gene therapy, which will be marketed in the United States with the brand name KEBILIDI™ (eladocagene exuparvovec-tneq), is indicated for the treatment of children and adults with AADC deficiency, including the full spectrum of disease severity. Launch preparations are well underway, with centers of excellence already identified and surgeons trained in the procedure to deliver the gene therapy. AADC deficiency is a highly morbid and life-shortening rare genetic disorder that results in the inability to synthesize dopamine, a neurotransmitter essential for motor function. KEBILIDI is a gene replacement therapy that is directly administered to the putamen of the brain through a stereotactic neurosurgical procedure. Clinical trial results demonstrate that following gene therapy, de novo synthesis of dopamine occurs, followed by the progressive acquisition of motor development milestones. KEBILIDI received accelerated approval based on the safety and clinical efficacy findings in the ongoing global clinical trial of the gene therapy (PTC-AADC-GT-002). Confirmatory evidence will be provided from the long-term follow up of patients already treated in the study. Along with the Biologics License Application approval, a Rare Disease Priority Review Voucher was granted. The company plans to monetize the voucher. About aromatic L-amino acid decarboxylase (AADC) deficiency: AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and suffering from the first months of life, affecting every aspect of life—physical, mental and behavioral.1-4 The suffering of children with AADC deficiency may be exacerbated by oculogyric crises, which are distressing, painful episodes that resemble seizures and are characterized by a stuck upward gaze, dystonia, and inconsolability. The lives of affected children are severely impacted and shortened.1 Ongoing physical, occupational and speech therapy, and interventions, including surgery, are also often required to manage potentially life-threatening complications, such as infections and severe feeding and breathing problems. About KEBILIDI™ (eladocagene exuparvovec-tneq): KEBILIDI is a recombinant adeno-associated virus serotype 2 (rAAV2)-based gene therapy, containing 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. Administration of KEBILIDI occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of pediatric and adult neurological disorders. The administration procedure is performed by a qualified neurosurgeon in centers specialized in stereotactic neurosurgery. KEBILIDI is authorized to be administered using the SmartFlow Neuro Cannula. KEBILIDI is an adeno-associated virus vector-based gene therapy indicated for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. This indication is approved under accelerated approval based on change from baseline in gross motor milestone achievement at 48 weeks post-treatment. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. KEBILIDI is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging. Skull maturity is needed for stereotactic neurosurgical administration of KEBILIDI. Procedure-Related Monitoring: Procedural complications have been reported after neurosurgery required for KEBILIDI administration. These events included respiratory and cardiac arrest which occurred within 24 hours of the neurosurgical procedure and during post-surgical care. KEBILIDI administration has the potential risk for additional procedure related adverse events including cerebrospinal fluid (CSF) leak, intracranial bleeding, neuroinflammation, acute infarction, and infection. Patients should be monitored for procedure related adverse events with KEBILIDI administration. Dyskinesia was reported after administration of KEBILIDI. All events were reported within 3 months of administration and 2 events required hospitalization. Monitor patients for signs and symptoms of dyskinesia after KEBILIDI treatment which may include involuntary movements of face, arm, leg, or entire body. These may present as fidgeting, writhing, wriggling, head bobbing or body swaying. The use of dopamine antagonists may be considered to control dyskinesia symptoms. 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%). Pediatric Use: The safety and efficacy of KEBILIDI have not been studied in pediatric patients younger than 16 months. · Geriatric Use: Clinical studies of KEBILIDI did not include patients 65 years of age and older.
