Fayuvi (rebisufligene etisparvovec-hopf) for MPS IIIA: AAV9 Single Infusion, Weight-Based Dose, Steroids, Liver/Platelet Monitoring

　　1.Position and Mechanism

　　Fayuvi(generic name rebisufligene etisparvovec-hopf;code UX111)is indicated for neurologic manifestations of pediatric mucopolysaccharidosis type IIIA(MPS IIIA,Sanfilippo A)with preserved neurodevelopment.A modified,nonpathogenic AAV9 vector delivers functional SGSH in a single intravenous infusion,restores sulfamidase,and lowers heparan sulfate accumulation in brain and somatic tissues.It does not replace rehabilitation,antiepileptic therapy,behavioral care,or nutritional support;advanced irreversible neurodegeneration limits expected benefit.

　　2.Dose and Product Calculation

　　Recommended single dose is 3.0×10¹³viral genomes(vg)/kg.For patients≤70kg use actual weight;for>70kg calculate as if 70kg.With product concentration 1.0×10¹³vg/mL and 2mL extractable per vial,required volume equals total target vg÷1.0×10¹³vg/mL,then convert to vials using 2mL per vial.Pharmacy should confirm extractable volume,dead space,and institutional compounding rules;do not estimate at home.Example only:20kg→6.0×10¹⁴vg→about 60mL product,then vial count per pharmacy worksheet.One infusion only,not repeated as a routine cycle.

　　3.Pre-Infusion Assessment

　　Baseline screening before eligibility and dosing:

　　Liver:ALT,AST,GGT,total bilirubin;add direct bilirubin,albumin,INR as needed.

　　Coagulation/platelets:platelet count,PT,aPTT;investigate abnormalities for liver disease,consumption,infection,or TMA before rescheduling.

　　Infection/immune risk:active infection,recent fever,immune status,and conditions that increase glucocorticoid risk including infection,hyperglycemia,psychiatric,peptic,or unstable hypertension issues.

　　Anti-AAV9 total binding antibody:if titer≥1:100,do not recommend treatment;lower or negative titers are interpreted by the gene-therapy center with prior AAV exposure and infusion plan.

　　Disease confirmation:SGSH biallelic pathogenic variants,sulfamidase deficiency or heparan sulfate metabolite evidence,cognitive/developmental assessment;ECG/echo per center.

　　4.Glucocorticoid Pretreatment

　　Start prednisone or prednisolone on the day before infusion at 1.0mg/kg/day for 8 weeks,then taper slowly over at least 4 weeks.Adjust duration or dose for ALT/AST rises,inflammatory signs,fever,or cytopenias.Persistent transaminase elevation may require prolonged steroids under gene-therapy/hepatology guidance.Do not stop steroids early because fever resolves,and do not extend unsupervised.In children monitor growth parameters,blood pressure,glucose,mood,and sleep.

　　5.Infusion Procedure

　　Use a dedicated peripheral venous line,infuse over about one hour at constant rate;no IV push,no bolus,no co-infusion through the same line with other products.Observe for hypersensitivity and infusion reactions:rash,lip/tongue swelling,wheeze,hypotension,chills,fever,vomiting.For mild-moderate reactions pause and,per clinician judgment,resume at reduced rate after control;for anaphylaxis or hemodynamic instability stop permanently and follow emergency protocols.Fever,vomiting,and transaminase rises after AAV9 must be distinguished from infection and vector hepatitis.

　　6.Post-Infusion Monitoring

　　Liver:ALT,AST,GGT,total bilirubin weekly for the first 2 weeks,then every 2 weeks until at least 2 weeks after glucocorticoids are fully tapered;if enzymes remain above baseline or keep rising,continue until recovery and evaluate TMA,viral hepatitis,and drug-induced liver injury.

　　Platelets:weekly for the first 4 weeks,then monthly through 6 months;add WBC,hemoglobin,and coagulation as indicated.

　　Additional:developmental/cognitive assessments,CSF heparan sulfate biomarkers,renal function and urinalysis/proteinuria,amylase/lipase,anti-AAV9 titers,and long-term registry follow-up.Watch TMA signals—anemia,falling platelets,elevated LDH,reticulocytosis,rising creatinine,hematuria/proteinuria.

　　7.Safety Priorities

　　Common adverse events include increased AST,nausea/vomiting,fever,decreased appetite,leukopenia,thrombocytopenia,and increased amylase.Label emphasis includes thrombotic microangiopathy;theoretical AAV genomic integration requires long-term oncologic surveillance.Return immediately for persistent abdominal pain,jaundice,hematuria/oliguria,altered consciousness,seizures,severe dehydrating vomiting,petechiae,or high fever.