Kebilidi

Kebilidi is a gene replacement therapy that is used to treat aromatic L-amino acid decarboxylase (AADC) deficiency and is administered directly into the brain.

• Kebilidi (eladocagene exuparvovec-tneq) is the first ever gene therapy in the U.S. to be approved that is administered directly into the brain.

Kebilidi’s mechanism of action involves correcting the underlying genetic defect in adults and children with AADC, a rare, life-threatening genetic disorder that results in the inability to make dopamine, a neurotransmitter essential for the regulation of movement. AADC is caused by genetic mutations in the dopa decarboxylase (DDC) gene and Kebilidi contains the human DDC gene connected to an adeno-associated viral vector which is directly administered into the putamen of the brain through a neurosurgical procedure. This results in AADC enzyme expression and the production of dopamine in the putamen.

Kebilidi gained FDA approval on Nov 13, 2024, under the accelerated approval designation. Continued approval may be contingent upon the clinical benefit of a change from baseline in gross motor milestone achievement at 48 weeks post-treatment being shown.

A child's skull must have reached maturity before Kebilidi is administered.

Before receiving Kebilidi, tell your healthcare provider about all your medical conditions including if you have:

• Heart or lung problems
• Movement disorders
• Low electrolyte levels
• Anemia
• Low blood pressure
• An infection
• Difficulty sleeping
• Are pregnant or intend to become pregnant
• Are breastfeeding or intend to breastfeed?

Kebilidi has not been studied in patients 65 years and older or children younger than 16 months.

Pregnancy

Kebilidi may harm an unborn baby. Sexually active females of reproductive potential should have a negative pregnancy test before administering Kebilidi.

Kebilidi is administered as 4 infusions directly into your brain in a single procedure by a healthcare provider.

• Each infusion takes approximately 27 minutes.

There is a risk of complications with the procedure, such as respiratory or cardiac arrest, leakage of your spinal fluid (CSF), bleeding inside your brain, inflammation inside your brain, stroke, or infection. Your healthcare provider will monitor you for these.

Uncontrolled muscle movements, including involuntary movements of the face, arm, leg, or entire body which may present as fidgeting, writhing, wriggling, head bobbing, or body swaying, may occur within 3 months of treatment with Kebilidi. Report any symptoms to your healthcare provider.

Vector Shedding. Temporary vector shedding of Kebilidi may occur for up to 3 weeks after administration. Your healthcare provider should practice proper hand hygiene and the appropriate handling of waste materials generated from dressings and/or any secretions (e.g., blood, nasal secretions, urine, stool, and CSF). Recommended procedures include storage of waste material in sealed bags before disposal and wearing gloves for dressings changes and waste disposal.

Patients should not donate blood, organs, tissues, or cells for transplantation.

The most common side effects of Kebilidi are:

• Uncontrolled, involuntary muscle movements, such as shakes, ticks, tremors, and full-body movements (dyskinesia)
• Fever
• Low blood pressure
• Low red blood cells (anemia)
• Excessive saliva production and dribbling
• Low potassium, phosphate, and magnesium levels
• Sleeplessness
• Complications with the procedure.

Serious side effects and warnings

Procedural complications, such as respiratory and cardiac arrest have been associated with Kebilidi administration. Your healthcare provider will monitor for these.

Dyskinesias (uncontrolled movement disorders) have occurred following Kebilidi treatment. Tell your healthcare provider if you or the person you are caring for experience uncontrolled shakes, tics, or tremors.

These are not all the side effects of Kebilidi. To report suspected side effects contact PTC 60 Therapeutics, Inc., at toll-free phone 1-866-562-4620 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Each Kebilidi single-dose 2 mL vial contains 2.8×1011 vg of eladocagene exuparvovec-tneq in an extractable volume of 0.5 mL of suspension.

Each mL of suspension contains a nominal concentration of 5.6×1011 vg of eladocagene exuparvovec-tneq.

PTC Therapeutics, Inc. makes Kebilidi.