First FDA-Approved Gene Therapy for AADC Deficiency

Kebilidi (eladocagene exuparvovec-tneq) is an adeno-associated virus (AAV) vector-based gene therapy given as a single stereotactic neurosurgical session of intraputaminal infusions. On the US Prescribing Information (revised 11/2024) it is 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 may depend on verification and description of clinical benefit in a confirmatory clinical trial.

Distinct path — not this label: Supportive care, dopamine agonists, MAO inhibitors, or other symptomatic medicines alone are not this intraputaminal gene-therapy label. Other neurotransmitter disorders without labelled AADC deficiency (biallelic DDC) are not this population. Today’s approved US intraputaminal gene-therapy pathway for AADC deficiency is PTC Therapeutics Kebilidi STN 125722.

The FDA approved the product on 13 November 2024 (FDA press announcement 14 November 2024). FDA product page lists STN 125722. USPI manufacturing footer: U.S. License No. 2168 to PTC Therapeutics, Inc., Warren, NJ. Associated pivotal NCT on the USPI: NCT04903288. FDA also authorised the ClearPoint SmartFlow Neuro Cannula (part numbers NGS-NC-01-EE or NGS-NC-02-EE) as the delivery device for Kebilidi.

Where this is taking place

Approved prescription route today: United States — FDA-labelled Kebilidi for AADC deficiency in adults and pediatrics who have achieved skull maturity on neuroimaging, administered only in a medical centre that specialises in stereotactic neurosurgery, using the FDA-authorised SmartFlow cannula, after genetic confirmation of biallelic DDC mutations. Product / AE contact on PI: PTC Therapeutics 1-866-562-4620. Patient / enrollment support materials for PTC Cares list 1-844-478-2227. This is a neurosurgery-centre gene therapy conversation — not a retail pharmacy pickup and not a DIY import.

In the US, the label requires a centre specialised in stereotactic neurosurgery and the authorised cannula. Treat named-centre lists as dynamic. Ask PTC Cares / a neurometabolic neurologist for the current designated-centre path. Do not assume every children’s hospital already infuses Kebilidi.

Outside the United States: At the time of writing, no confirmed Health Canada Notice of Compliance / DIN for Kebilidi. Do not import on your own. Historical research or overseas treatment experience is not the same sentence as a Canadian or other foreign marketing authorisation for your home regulator.

Study 1 — NCT04903288 (ClinicalTrials.gov: active but no longer taking new patients; primary completion actual 22 May 2023; study completion estimated 30 Apr 2028) — Open-label, single-arm study in pediatric patients with genetically confirmed severe AADC deficiency who had achieved skull maturity. Labelled commercial access is through designated neurosurgery centres and PTC Cares. A research record that is active but no longer taking new patients is not walk-in commercial enrolment. Confirmatory obligations remain under accelerated approval.

The practical prescription route in the US is a pediatric neurology / neurometabolic / neurosurgery team working with PTC Cares to confirm AADC genetics, document skull maturity, plan imaging and stereotactic infusion, and arrange payer / travel logistics.

Approval matrix

Access by country

• United States: Ask a pediatric neurology / neurometabolic / stereotactic neurosurgery clinician about referral for FDA-labelled Kebilidi. Labelled 13 November 2024 (accelerated). Path: confirm AADC deficiency due to biallelic DDC mutations → confirm skull maturity on neuroimaging → designated stereotactic centre + SmartFlow cannula → thaw / prepare within timing windows on the PI → four intraputaminal infusions totaling 1.8×10¹¹ vg in one session → monitor for procedural complications and dyskinesia. PTC Cares enrollment: 1-844-478-2227. Suspected adverse reactions: PTC 1-866-562-4620 or FDA MedWatch 1-800-FDA-1088. No list price or copay dollars in this article. This is US labelled supply through specialised centres, not a DIY import.

• Canada: Kebilidi authorisation not confirmed. Ask the Canadian neurometabolic / neurosurgery clinic what legal paths exist in Canada when a Canadian Kebilidi label does not yet exist.

• European Union / United Kingdom / Australia / Japan / other countries: Confirm your local regulator’s current status with the treating centre. A US vial is not a foreign pack. Do not import on your own.

• If your regulator has not authorised it: do not import on your own. Ask the local clinician about documented special-access / named-patient rules, referral to a centre in a labelled country, or waiting.

Who is eligible (from the US label)

This is an intraputaminal AAV gene-therapy conversation on the Prescribing Information — not a home infusion, and not for people who have not achieved skull maturity.

United States (USPI, revised November 2024):

• Indication: Adult and pediatric patients with AADC deficiency.
• Important dosing prerequisite: Confirm AADC deficiency due to biallelic mutations in the DDC gene.
• Recommended dose: Total 1.8×10¹¹ vg (0.32 mL) as four 0.08 mL (0.45×10¹¹ vg) infusions — two anterior and two posterior putamen — at 0.003 mL/min for 27 minutes per site, in a single stereotactic surgery, using only an FDA-authorised intraparenchymal cannula (SmartFlow NGS-NC-01-EE or NGS-NC-02-EE).
• Contraindications: Patients who have not achieved skull maturity assessed by neuroimaging.
• Warnings: Procedural complications of neurosurgery (including respiratory and cardiac arrest after administration); dyskinesia (dopamine antagonists may be used to control symptoms).
• Most common adverse reactions (≥15%): dyskinesia, pyrexia, hypotension, anemia, salivary hypersecretion, hypokalemia, hypophosphatemia, insomnia, hypomagnesemia, procedural complications.
• Pediatrics: Established in the Study 1 pediatric cohort (median age 2.8 years, range 1.3–10.8); not studied in patients younger than those enrolled / without skull maturity.
• Geriatrics: Not studied in patients ≥65.
• Supply: Single-dose vial with extractable 0.5 mL containing 2.8×10¹¹ vg (nominal 5.6×10¹¹ vg/mL); carton NDC 52856-601-01, vial NDC 52856-601-11. Store frozen ≤ −65°C; use within 6 hours of starting thaw (infusion itself ~4 hours; max thaw-to-completion 10 hours on PI).

Not labelled on the sources checked for this article:

• Use without confirmed biallelic DDC AADC deficiency.
• Use before skull maturity.
• Canadian (and several other) marketing authorisations (not confirmed here).
• Treating accelerated approval as already-verified lifelong clinical benefit.
• Treating research that is active but no longer taking new patients as open commercial trial recruitment.

What the pivotal evidence showed (USPI)

Use the USPI for a prescription conversation. Journals are supportive reading.

Study 1 — NCT04903288 (USPI §14):

• 13 pediatric patients received a single total dose of 1.8×10¹¹ vg as four intraputaminal infusions. Median age 2.8 years (range 1.3–10.8). 12/13 had the severe phenotype (no motor milestone at baseline); one had a “variant” severe phenotype (sit with assistance but lack of head control).
• Week 48 motor assessment completed for 12 of 13 (one discontinued before Week 48).
• 8/12 (67%) achieved a new gross motor milestone at Week 48 (full head control in 3; sitting with/without assistance in 2; walking backwards in 2; sit unassisted in the variant-phenotype patient). The two who achieved walking backwards were treated before age 2.
• Comparison cohort: 0/43 untreated severe natural-history patients had documented motor milestone achievement at last assessment (median age 7.2 years, range 2–19).
• Accelerated approval is based on these early motor-milestone changes; confirmatory verification of clinical benefit remains required.

How to talk with a doctor

Bring this page and ask a neurology / neurometabolic / neurosurgery clinician:

1. “We have genetically confirmed AADC deficiency (biallelic DDC). Has skull maturity been documented, and is labelled US Kebilidi the path to discuss?”
2. “Which stereotactic neurosurgery centre are you referring to, and what is the current PTC Cares intake step (1-844-478-2227)?”
3. “What are the imaging, cannula, and post-procedure monitoring plans for breathing, heart rhythm, and dyskinesia?”
4. “How should we understand accelerated approval and the confirmatory trial still underway?”
5. If outside the US: “Has our regulator authorised Kebilidi, or what legal special-access options exist?”

Who is involved (from primary sources)

• License holder / manufacturer: PTC Therapeutics, Inc., Warren, NJ 07059 USA — U.S. License 2168 (USPI).
• Patient support / enrollment: PTC Cares — 1-844-478-2227 (enrollment / start-form materials).
• Pivotal program: Study 1 NCT04903288.
• Delivery device (FDA-authorised for Kebilidi): ClearPoint SmartFlow Neuro Cannula (NGS-NC-01-EE / NGS-NC-02-EE); device authorisation granted to ClearPoint Neuro, Inc. (FDA press).
• Product / AE contact on USPI: PTC Therapeutics 1-866-562-4620.

Names and roles above are limited to what appears on the primary sources cited. Contacts not listed on those sources are omitted.

Sources

• FDA press announcement, 14 Nov 2024 (approval date 13 Nov 2024 on orphan/marketing materials)
• FDA KEBILIDI product page STN 125722
• US Package Insert — KEBILIDI (Rev 11/2024)
• ClinicalTrials.gov NCT04903288
• PTC Cares / Kebilidi enrollment and start-form materials (support phone)

Authorized is not funded. Not medical advice.