Eladocagene Exuparvovec-Tneq
FDA Drug Information • Also known as: Kebilidi
- Brand Names
- Kebilidi
- Route
- INTRACEREBRAL
- Dosage Form
- SUSPENSION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION KEBILIDI (eladocagene exuparvovec-tneq) is a gene therapy product that expresses the human aromatic L-amino acid decarboxylase enzyme (hAADC). It is a recombinant adeno-associated virus serotype 2 (rAAV2) based vector containing the complementary DNA of the human DDC gene under the control of the cytomegalovirus immediate-early promoter. Eladocagene exuparvovec-tneq is produced in human embryonic kidney cells by recombinant DNA technology. KEBILIDI is a sterile suspension administered by bilateral intraputaminal infusion in one surgical session at two sites (anterior and posterior) per putamen. Each single-dose 2 mL vial contains 2.8×10 11 vg in an extractable volume of 0.5 mL of suspension. Each mL of suspension contains 5.6×10 11 vg. Patients will receive a total dose of 1.8×10 11 vg delivered as four 0.08 mL (0.45×10 11 vg) infusions (two per putamen). KEBILIDI is provided in a single-dose 2 mL vial containing a clear to slightly opaque, colorless to faint white liquid, free of visible particulates following thaw from its frozen state. The excipients include potassium chloride (3 mM), sodium chloride (337 mM), potassium dihydrogen phosphate (2 mM), disodium hydrogen phosphate (8 mM), and poloxamer 188 (0.001%).
What Is Eladocagene Exuparvovec-Tneq Used For?
1 INDICATIONS AND USAGE KEBILIDI (eladocagene exuparvovec-tneq) is an adeno-associated virus (AAV) 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 the change from baseline in gross motor milestone achievement at 48 weeks post treatment [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. KEBILIDI is an adeno-associated virus (AAV) 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. ( 1 , 14 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For single-dose intraputaminal infusion only. For single-dose intraputaminal infusion only. Recommended dose: 1.8×10 11 vector genomes (vg). ( 2.2 ) Brain imaging for stereotactic planning and intraoperative navigation should be done prior to the procedure. ( 2.4 ) Post stereotactic registration, mark the entry point on the skull. Surgical access through the skull bone and dura should be performed. ( 2.4 ) Administer a total dose of 1.8×10 11 vg (0.32 mL total volume) delivered as four 0.08 mL (0.45×10 11 vg) infusions (two sites per putamen-anterior and posterior) at a rate of 0.003 mL/minute (0.18 mL/hour) for a total of 27 minutes per site, administered in a single stereotactic surgery using a cannula that is FDA-authorized for intraparenchymal infusion. ( 2.2 , 2.4 ) 2.1 Important Dosing Information Confirm patient has AADC deficiency due to biallelic mutations in the DDC gene. Strictly observe aseptic technique during preparation and administration of KEBILIDI. KEBILIDI should be administered in a medical center which specializes in stereotactic neurosurgery. Administer KEBILIDI only using an FDA-authorized cannula for intraparenchymal infusion (i.e., ClearPoint SmartFlow Neuro Cannula Part Number NGS-NC-01-EE or NGS-NC-02-EE). Use of the syringe (i.e., connecting the syringe to the syringe pump and priming of the cannula) should begin within 6 hours of starting product thaw KEBILIDI is intended to be administered with an infusion pump capable of infusing at a rate of 0.003 mL/min. 2.2 Recommended Dose KEBILIDI is administered as four intraputaminal infusions in a single stereotactic neurosurgical procedure as per the recommended dose shown in Table 1 . Table 1: Recommended Dose of KEBILIDI Total Recommended Dose 1.8x10 11 vg (0.32 mL) Total number of infusions 4 Volume (dose) per infusion 0.08 mL (0.45x10 11 vg) Location of infusions 2 in anterior putamen, 2 in posterior putamen Infusion rate at each target point 0.003 mL/min Dose duration for infusion at each target point 27 minutes 2.3 Preparation Thawing KEBILIDI Vial Coordinate timing of KEBILIDI thaw and infusion. KEBILIDI should be used within 6 hours of starting product thaw. Infusion of KEBILIDI takes 4 hours. The maximum time from thaw to completion of infusion should be no more than 10 hours. Thaw the KEBILIDI vial upright at room temperature before use. The contents of the vial will thaw in approximately 15 minutes at room temperature. Do not thaw or warm the vial any other way. Gently invert the vial 3 times. Do not shake the vial. Inspect the fully thawed KEBILIDI vial after mixing. KEBILIDI should be inspected visually for particulate matter, and discoloration prior to administration. KEBILIDI is clear to slightly opaque. The color of KEBILIDI should be a colorless to faint white suspension Do not use if particulates, or discoloration are visible in the suspension. Preparing KEBILIDI in Syringe Gather supplies listed in Table 2 for preparation:...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥15%) were dyskinesia, pyrexia, hypotension, anemia, salivary hypersecretion, hypokalemia, hypophosphatemia, insomnia, hypomagnesemia, and procedural complications. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact PTC Therapeutics, Inc at toll-free phone 1 866 562 4620 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflects exposure to KEBILIDI in 13 pediatric patients with genetically confirmed AADC deficiency who received a single dose of 1.8×10 11 vg. The median duration of follow-up was 72 weeks (range 23 to 109 weeks) [see Clinical Studies ( 14 )] . The most common adverse reactions (incidence ≥15%) are summarized in Table 3 . Table 3: Adverse Reactions in ≥15% of Patients in Study 1 * Procedural complications included respiratory and cardiac arrest. Adverse Reaction Patients Treated with KEBILIDI N=13 (%) Dyskinesia 10 (77%) Pyrexia 5 (38%) Hypotension 4 (31%) Anemia 4 (31%) Salivary hypersecretion 3 (23%) Hypokalemia 3 (23%) Hypophosphatemia 3 (23%) Insomnia 3 (23%) Hypomagnesemia 2 (15%) Procedural complications * 2 (15%) Other clinically significant adverse reaction includes worsening in duration and frequency of oculogyric crises during hospitalization following administration of KEBILIDI reported in one patient.
Contraindications
4 CONTRAINDICATIONS KEBILIDI is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging. Skull maturity is needed for stereotactic neurosurgical administration of KEBILIDI. Patients who have not achieved skull maturity assessed by neuroimaging. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no clinical data from the use of KEBILIDI in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with KEBILIDI. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied KEBILIDI is supplied in a single-dose 2 mL vial containing sterile, clear to slightly opaque, colorless to faint white liquid free of visible particulates, following thaw from its frozen state. Each KEBILIDI (eladocagene exuparvovec-tneq) vial contains 2.8×10 11 vg of eladocagene exuparvovec-tneq in an extractable volume of 0.5 mL of suspension. Each mL of suspension contains a nominal concentration of 5.6×10 11 vg of eladocagene exuparvovec-tneq. Package (carton): NDC Number 52856-601-01 Container (vial): NDC Number 52856-601-11 Storage and Handling Store and transport frozen at ≤-65°C (-85°F). Keep the vial in the supplied carton. Thaw KEBILIDI prior to administration. If not used immediately, store at room temperature (up to 25°C [77°F]) and use within 6 hours of starting product thaw [see Dosage and Administration ( 2.3 )] . Do not refreeze vial once thawed.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.