First FDA-Approved Gene Therapy for Sanfilippo Syndrome Type A

Fayuvi (rebisufligene etisparvovec-hopf) is an adeno-associated virus (AAV) vector-based gene therapy given as a single intravenous infusion. On the US Package Insert (revised 09/2026) it is indicated for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A) in pediatric patients with preserved neurodevelopmental function.

This is a traditional FDA biologic approval (CBER). The FDA approved STN BL 125845/0 on 17 September 2026. Approval letter authorizes marketing under Ultragenyx’s existing U.S. License No. 2040. Letter attention: Jad Adaimi. Associated NCT numbers on the letter: NCT02716246, NCT04360265, NCT04088734. FDA news materials describe Orphan Drug, Fast Track, and Breakthrough Therapy designations. Company materials describe standard full approval and a Priority Review Voucher upon approval.

Distinct path — not this carton (fact-only): Supportive / symptomatic care alone is not this gene-therapy carton. Other mucopolysaccharidosis types (including other Sanfilippo subtypes) are not this labelled population. Today’s US labelled gene-therapy door for neurologic manifestations of MPS IIIA in pediatric patients with preserved neurodevelopmental function is Ultragenyx Fayuvi STN 125845.

Manufactured for US supply under Ultragenyx’s licence (company materials describe US manufacturing including Bedford, MA and Andelyn Biosciences, Columbus, OH).

Where this is taking place

Commercial labelled door today: United States — FDA-labelled Fayuvi for pediatric MPS IIIA with preserved neurodevelopmental function, administered at a Qualified Treatment Center (QTC) with specialized gene-therapy capability, after anti-AAV9 antibody testing, baseline liver and coagulation labs, planned corticosteroid prophylaxis, and UltraCare / payer logistics. Company launch guidance at approval: commercial product expected to ship to QTCs within roughly 30–60 days of 17 September 2026 — treat that as a launch window, not a guarantee every centre is ready every day. Company materials point to fayuvi.com for QTC details as the site comes online. This is a centre-administered one-time gene therapy conversation — not a retail pharmacy pickup and not a DIY import.

Outside the United States: As of this draft, no confirmed Health Canada Notice of Compliance, European Commission marketing authorisation, MHRA licence, TGA listing, Swissmedic authorisation, or PMDA/MHLW licence for Fayuvi / rebisufligene etisparvovec. Do not import on your own.

Study 1 / Transpher A — NCT02716246 — Multicenter, open-label, single-arm, single-dose, dose-escalation gene-transfer study. Lead sponsor on CT.gov: Ultragenyx Pharmaceutical Inc. CT.gov status at draft time: RECRUITING (estimated enrolment 36) — that status can coexist with labelling from completed efficacy cohorts; treat pivotal labelled evidence as complete for the mITT analysis, not as a promise of open commercial trial slots. Locations listed include the United States, Spain, and Australia. Long-term follow-up: NCT04360265 (ClinicalTrials.gov: ENROLLING_BY_INVITATION). Honesty: Labelled commercial access is through QTCs — completed or ongoing study cohorts are not the same sentence as walk-in enrolment, and foreign trial sites are not a foreign marketing authorisation.

The practical commercial door in the US is a metabolic genetics / lysosomal-storage / gene-therapy team working with a Qualified Treatment Center to confirm MPS IIIA, document preserved neurodevelopmental function, complete anti-AAV9 testing and liver/platelet labs, plan infusion + steroids, and arrange UltraCare / payer logistics.

Approval matrix

Access by country

• United States: Ask a metabolic genetics / lysosomal-storage / gene-therapy team about referral to an Ultragenyx Qualified Treatment Center for FDA-labelled Fayuvi. Labelled 17 September 2026 for neurologic manifestations of MPS IIIA in pediatric patients with preserved neurodevelopmental function. Recommended dose: 3.0×10¹³ vg/kg as a single IV infusion over about 1 hour (concentration 1.0×10¹³ vg/mL; 2 mL extractable volume per vial; kits 5–105 vials by weight; >70 kg → dose at 70 kg). Not recommended if anti-AAV9 total binding antibody titer ≥1:100 (FDA-authorized companion test not currently available — contact Ultragenyx for testing information). Start oral corticosteroids 1 day before infusion (1.0 mg/kg/day prednisone/prednisolone for 8 weeks, then taper ≥4 weeks). Monitor liver enzymes, platelets, and clinical signs of TMA / infusion reactions per PI. Vial NDC 69794-300-01; shipped frozen ≤ −60 °C. UltraCare Gene Therapy Guides: 1-888-756-8657 (Mon–Fri 9 a.m.–8 p.m. ET per company materials) / ultracaresupport.com. Suspected adverse reactions or malignancy reports: Ultragenyx 1-888-756-8657 or FDA MedWatch 1-800-FDA-1088. No list price or copay dollars in this article. This is US labelled supply through QTCs, not a DIY import.

• Canada: Fayuvi authorisation not confirmed. Ask the Canadian metabolic / genetics clinic what legal paths exist in Canada when a Canadian Fayuvi label does not yet exist.

• European Union / United Kingdom / Australia / Japan / other countries: Regulator authorisation not confirmed in this draft. Open or completed trial sites are not a commercial foreign carton. 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 — without treating a US kit as a foreign carton.

Who is eligible (from the US label)

This is a pediatric MPS IIIA with preserved neurodevelopmental function conversation on the Package Insert — one-time IV gene therapy — not a promise for every Sanfilippo subtype or for children without preserved function.

United States (Package Insert, revised September 2026):

• Indication: Treatment of neurologic manifestations of MPS IIIA (Sanfilippo syndrome type A) in pediatric patients with preserved neurodevelopmental function.
• Recommended dosage: 3.0×10¹³ vg/kg single IV infusion ~1 hour.
• Antibody selection: Administration not recommended if anti-AAV9 total binding antibody titer ≥1:100.
• Contraindications: None (USPI §4).
• Warnings: Hepatotoxicity; thrombocytopenia; TMA (monitor even though no FAYUVI TMA cases in clinical studies); hypersensitivity / infusion reactions; theoretical malignancy from AAV integration — report malignancies to Ultragenyx; pregnancy (negative serum pregnancy test required in females of childbearing potential; do not treat pregnant patients); vector shedding precautions about 3 months.
• Most common adverse reactions (≥5% at recommended dose, N=27): liver enzyme increased (85%), vomiting (67%), abnormal behavior (56%), diarrhea (48%), pyrexia (41%), white cell count decreased (30%), Cushingoid features (30%), decreased appetite (22%), platelet count decreased (19%), anemia (19%), and others listed in PI Table 3.
• mITT efficacy framing (USPI): Study 1 patients at recommended dose who were ≤2 years at treatment, or >2 years with Cognitive Developmental Quotient (DQ) ≥60 (mild or moderate neurodevelopmental impairment) and baseline anti-AAV9 <1:100.
• Vaccines: Avoid vaccines 30 days before treatment (and corticosteroid use) and while on corticosteroids, per PI.
• Pediatrics: Established in pediatric patients in Studies 1–3 (mean age at treatment in safety set about 38.5 months; range from months to years on PI). Geriatric use: not studied in ages 65+.

Not labelled on sources confirmed for this draft:

• Adults / geriatric patients as a labelled population.
• Patients with elevated anti-AAV9 titers (≥1:100) — administration not recommended.
• Other MPS / Sanfilippo subtypes (IIIB/C/D, etc.).
• EU, UK, Canadian, Japanese, Australian, or Swiss Fayuvi marketing authorisations (not confirmed here).
• Treating CT.gov “recruiting” status as walk-in commercial enrolment at every site.

What the pivotal study showed (USPI)

Use the Package Insert for a prescription conversation. Company materials are supportive reading.

Study 1 — NCT02716246 + Study 2 LTFU — NCT04360265 (USPI §14):

• Open-label, single-arm program vs external natural-history control.
• mITT (N=17) at recommended dose with preserved-function framing above vs natural history (N=27).
• Primary cognitive framing: mean change in Bayley-III Cognitive raw score from chronological age 24 to 60 months.

Median follow-up across studies about 4.2 years (range 2.9–7.8). CSF heparan sulfate reductions also described on PI (supportive biomarker framing).

How to talk with a doctor

Bring this page and ask a metabolic genetics / lysosomal-storage / gene-therapy clinician:

1. “Does my child have genetically confirmed MPS IIIA, and does the labelled preserved neurodevelopmental function gate fit?”
2. “How do we arrange anti-AAV9 antibody testing and referral to a Qualified Treatment Center?”
3. “What is the steroid plan before and after infusion, and how will you monitor liver enzymes and platelets?”
4. “Can we enroll with UltraCare Gene Therapy Guides for insurance and logistics?”
5. If outside the US: “Has our regulator authorised Fayuvi, or what legal special-access options exist?”

Who is involved (from primary sources)

• Sponsor / manufacturer: Ultragenyx Pharmaceutical Inc. (U.S. License No. 2040; BLA letter address Brisbane, CA).
• Pivotal program: Study 1 / Transpher A (NCT02716246); long-term follow-up (NCT04360265); additional NCT on letter 04088734.
• Investigator named in company announcement: Kevin M. Flanigan, M.D., director of the Center for Gene Therapy at Nationwide Children’s Hospital — principal investigator on the study that led to approval (Ultragenyx 17 Sep 2026 announcement).
• Patient support (company): UltraCare Gene Therapy Guides — 1-888-756-8657; ultracaresupport.com; fayuvi.com (QTC details as site launches).

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

Sources

1. FDA — Package Insert, Fayuvi (rebisufligene etisparvovec-hopf), revised 09/2026 (https://www.fda.gov/media/194920/download).
2. FDA — BLA Approval Letter STN BL 125845/0, 17 September 2026 (https://www.fda.gov/media/194921/download).
3. FDA press announcement — First gene therapy for pediatric Sanfilippo syndrome type A, 17 September 2026.
4. FDA CBER product page — FAYUVI (rebisufligene etisparvovec-hopf).
5. Ultragenyx announcement — FAYUVI approval, 17 September 2026 (UltraCare / QTC / 30–60 day ship window).
6. ClinicalTrials.gov — NCT02716246, NCT04360265.

Not medical advice. Talk with a clinician who knows the full history before any treatment decision. Authorized is not funded.