Kebilidi Approved for AADC Deficiency

On Nov. 13, 2024, PTC Therapeutics announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval of Kebilidi^™ (eladocagene exuparvovec-tneq). This is the first gene therapy directly administered to the brain and is indicated for the treatment of adult and pediatric patients with aromatic 13 L-amino acid decarboxylase (AADC) deficiency. Kebilidi is a recombinant adeno-associated virus vector (AAV) gene therapy that uses human DNA to replace AADC. It is administered during surgery as four infusions, two per putamen – a part of the brain. PTC Therapeutics has identified centers of excellence and surgeons to train although a specific launch date and cost are unknown at this time. For complete prescribing information, look here. 

At a Glance

• Brand Drug: Kebilidi^™ (eladocagene exuparvovec-tneq)
• Manufacturer: PTC Therapeutics
• Date Approved: Nov. 13, 2024
• Indication: For the treatment of adult and pediatric patients with AADC deficiency
• Dosage Forms Available: An AAV vector-based gene therapy infused through a surgical procedure directly into the putamen, parts of the brain that affect learning and movement. It will be delivered as four infusions, two per putamen in one surgical session. The concentration of the Kebilidi suspension is 5.6 x 10¹¹ vg/mL.
• Launch Date: The specific launch date is unknown, however, preparation has begun with centers of excellence identified and surgeons being trained.
• Estimated Annual Cost: Cost information is not known at this time.
• AACD deficiency is a rare, fatal genetic disorder that often presents symptoms in the first few months of life. It results in low energy, involuntary movements, poor sleep, weak or stiff muscles, and the failure to reach typical achievements, such as learning to sit up, talk, and walk. Many patients have oculogyric crises, which are typified by uncontrollable eye, head, and neck movements, intense irritability, muscle spasms, pain, and seizures. Oculogyric crises are painful and tend to occur every few days and can last for several hours. AADC deficiency also causes dysfunction of the autonomic nervous system causing many patients to experience low blood sugar, low blood pressure, or excessive sweating.
• AACD deficiency is extremely rare; about 100 patients with this disease have been identified in the US, with a total of 350 patients reported in all medical literature. It results from mutations in the dopa decarboxylase (DDC) gene, which causes shortages of the enzyme AADC. As a result, levels of dopamine and serotonin, two neurotransmitters that help pass information between nerve cells, are decreased. Children who have severe deficiencies of AADC seldom survive into their teens.
• This accelerated approval was based on findings from an ongoing global clinical trial showing the production of dopamine and motor development milestones being met after gene therapy administration. In 2021, PTC Therapeutics presented an analysis of three open-label clinical trials that showed children treated demonstrated motor function improvements that were sustained, including a decrease in oculogyric crises. Long-term follow-up from the ongoing trial is expected to provide confirmatory evidence.
• There are no FDA-approved treatments to correct AACD deficiency and no other pipeline drugs in late-phase development.
• Current treatment focuses on increasing available neurotransmitters and relieving symptoms. This may include vitamin B6 (pyridoxine) because it enhances any AADC production that the patient has. To increase dopamine, drugs such as bromocriptine are used off-label and monoamine oxidase inhibitors, including selegiline and tranylcypromine, may be used to delay the metabolism of dopamine and serotonin. Patients may also need medications to control seizures and manage blood pressure and blood sugar.