Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action KEBILIDI is a recombinant adeno-associated virus serotype 2 (rAAV2) based gene therapy designed to deliver a copy of the DDC gene which encodes the AADC enzyme. Intraputaminal infusion of KEBILIDI results in AADC enzyme expression and subsequent production of dopamine in the putamen. 12.2 Pharmacodynamics Homovanillic Acid in Cerebrospinal Fluid In Study 1, homovanillic acid (HVA), a downstream metabolite of dopamine, in cerebrospinal fluid (CSF) was measured at baseline, Week 8, and Week 48 using a high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In all patients of Study 1, an increase in CSF HVA levels from baseline was observed at Week 8 and Week 48 ( Table 4 ).
Indications
- 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.
Common Doses
- 0.32 mL
- 0.08 mL
- 0.003 mL
- 0.18 mL
Dosage
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.
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 )
Side Effects
- 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...
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.