The U.S. Food and Drug Administration approved Kebilidi (eladocagene exuparvovec-tneq), a gene therapy based on an adeno-associated virus vector that is recommended for the treatment of patients with aromatic L-amino acid decarboxylase (AADC) deficiency in both adults and children. kebilidi is the first gene therapy for AADC deficiency to receive FDA approval .
Aromatic L-amino acid decarboxylase deficiency is a rare genetic disorder that affects the production of some neurotransmitters, which are chemical messengers that allow cells in the body’s nervous system to communicate with each other. Affected individuals may experience symptoms such as delays in gross motor function (head control, sitting, standing, and walking), hypotonia (weak muscle tone), and developmental and cognitive delays.
Kebilidi is administered via four infusions in one surgical session into a large structure in the brain involved in motor control. Kebilidi should be administered in a medical center that specializes in pediatric stereotactic neurosurgery — a technique that uses imaging and special equipment to deliver therapies to specific areas in the brain. After infusion of Kebilidi, treatment results in the expression of AADC and subsequent increase in the production of dopamine, a critical neurotransmitter in the brain associated with movement, attention, learning and memory.
The safety and effectiveness of Kebilidi were demonstrated in an open-label, single-arm clinical study in 13 pediatric patients with confirmed diagnosis of AADC deficiency.
Kebilidi was approved using the Accelerated Approval pathway. Accelerated approval allows the FDA to approve certain products for serious or life-threatening conditions based on evidence of a product’s effect on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict clinical benefit. In the FDA’s evaluation of Kebilidi for accelerated approval, evidence of effectiveness is based on early improvements in gross motor function measured at 48 weeks after treatment. Continued approval for this indication may be contingent upon verification and description of clinical benefit of the product, such as the durability of the improvements, in a confirmatory clinical trial. A confirmatory trial is ongoing to verify Kebilidi’s clinical benefit. The application received Priority Review and Orphan Drug designation, and was granted a rare pediatric disease priority review voucher by the FDA.
The FDA also authorized the SmartFlow Neuro Cannula, an infusion tube inserted into a target in the brain (parenchymal tissue), to deliver Kebilidi. The SmartFlow Neuro Cannula is currently the only FDA authorized device indicated for use to administer Kebilidi. The FDA granted authorization of the SmartFlow Neuro Cannula to ClearPoint Neuro, Inc.
The most common adverse reactions of Kebilidi are dyskinesia (involuntary muscle movements), fever, low blood pressure, anemia (low red blood cell count), increased saliva production, insomnia, low levels of potassium, phosphate, and/or magnesium, and procedural complications such as respiratory and cardiac arrest. It is also contraindicated in patients who have not achieved skull maturity assessed by neuroimaging.
Learn more: FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency | FDA
