Kebilidi
(Eladocagene Exuparvovec-Tneq)Kebilidi Prescribing Information
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
The efficacy of KEBILIDI was evaluated in one open-label, single arm study (Study 1; NCT04903288). The study enrolled pediatric patients with genetically confirmed, severe AADC deficiency who had achieved skull maturity assessed with neuroimaging. The main efficacy outcome measure was gross motor milestone achievement evaluated at week 48 and assessed using the Peabody Developmental Motor Scale, Second Edition (PDMS-2). Patients treated with KEBILIDI were compared to an external untreated natural history cohort of 43 pediatric patients with severe AADC deficiency who had at least one motor milestone assessment after 2 years of age.
A total of 13 patients received a single total dose of 1.8×1011vg of KEBILIDI given as four intraputaminal infusions in a single stereotactic neurosurgical procedure. The demographic characteristics of the population were as follows: the median age was 2.8 years (1.3 to 10.8 years), 7 patients (54%) were female, 10 patients (77%) were Asian, 2 patients (15%) were White, and 1 patient was of “other” race. Twelve of the 13 patients had the severe phenotype of AADC deficiency, defined as having no motor milestone achievement at baseline and no clinical response to standard of care therapies. The one remaining patient had a “variant” of the severe disease phenotype, with the ability to sit with assistance but with lack of head control.
Gross motor milestone achievement at Week 48 was assessed in 12 of the 13 patients treated in Study 1 (one patient dropped out of the study prior to Week 48).
Eight (67%) of the 12 treated patients achieved a new gross motor milestone at week 48: 3 patients achieved full head control, 2 patients achieved sitting with or without assistance, 2 patients achieved walking backwards and the patient with the “variant” severe phenotype was able to sit unassisted. The two patients who achieved walking backwards at week 48 were treated before 2 years of age. The four patients who were unable to achieve new gross motor milestones at week 48 were treated between the ages of 2.8 and 10.8 years. In comparison, none of the 43 untreated patients with the severe phenotype had documented motor milestone achievement at last assessment at a median age of 7.2 years (range 2 to 19 years).
KEBILIDI is a sterile suspension for intraputaminal infusion. Each single-dose vial contains 2.8×1011 vg/0.5 mL (nominal concentration of 5.6×1011 vg/mL) of KEBILIDI and each 2 mL vial contains an extractable volume of 0.5 mL.
Following product thaw, the suspension for infusion is a clear to slightly opaque, colorless to faint white liquid, free of visible particulates
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 2.8×1011vg of eladocagene exuparvovec-tneq in an extractable volume of 0.5 mL of suspension. Each mL of suspension contains a nominal concentration of 5.6×1011vg of eladocagene exuparvovec-tneq.
Package (carton): NDC Number 52856-601-01
Container (vial): NDC Number 52856-601-11
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
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.
KEBILIDI is contraindicated in patients who have not achieved skull maturity assessed by neuroimaging. Skull maturity is needed for stereotactic neurosurgical administration of KEBILIDI.
- Procedural complications: Monitor patients for procedural complications for neurosurgery, including events of respiratory and cardiac arrest after administration of KEBILIDI. ()
5.1 Procedural ComplicationsProcedural complications have been reported after neurosurgery required for KEBILIDI administration. These events included respiratory and cardiac arrest which occurred within 24 hours of the neurosurgical procedure and during post-surgical care
[see Adverse Reactions (6)]. KEBILIDI administration has the potential risk for additional procedure related adverse events including cerebrospinal fluid (CSF) leak, intracranial bleeding, neuroinflammation, acute infarction, and infection.Monitor patients for procedure related adverse events with KEBILIDI administration, including continuous cardiorespiratory monitoring during hospitalization.
- Dyskinesia: Monitor patients for dyskinesia after treatment with KEBILIDI. The use of dopamine antagonists can be used to control dyskinesia symptoms. ()
5.2 DyskinesiaDyskinesia was reported after administration of KEBILIDI. All events were reported within 3 months of administration and 2 events required hospitalization
[see Adverse Reactions (6)].Monitor patients for signs and symptoms of dyskinesia after KEBILIDI treatment which may include involuntary movements of face, arm, leg, or entire body. These may present as fidgeting, writhing, wriggling, head bobbing or body swaying. The use of dopamine antagonists may be considered to control dyskinesia symptoms.