FAYUVI Suspension for infusion Ref.[116937] Active ingredients: Rebisufligene etisparvovec

2.1 Dose

For single-dose intravenous infusion only.

The recommended dose of FAYUVI is 3.0 × 10¹³ vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous infusion.

Table 1. Recommended Dosing:

^a Dose volume is calculated using the upper limit of the patient weight range, rounded up to the nearest 2 mL.
^b Patients weighing >70 kg will be dosed at the 70 kg weight.

Prior to FAYUVI Infusion:

• Due to the concern for potential hepatotoxicity, assess liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin] and liver-related medical history [see Warnings and Precautions (5.1)].
• Due to the concern for potential thrombocytopenia, assess platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT).
• Evaluate patients for conditions that may increase the risks associated with corticosteroid therapy. Delay treatment until clinically significant infections are adequately controlled.
• Perform testing for the presence of anti-AAV9 antibodies. FAYUVI administration is not recommended for patients with elevated anti-AAV9 total binding antibody titers (≥ 1:100) [see Clinical Pharmacology (12.6)]. An FDA-authorized test for the detection of anti-AAV9 total binding antibodies is not currently available. For information regarding anti-AAV9 testing, contact Ultragenyx Pharmaceutical Inc. at 1-888-756-8657. Currently available tests may vary in accuracy and design.
• Starting 1 day prior to FAYUVI infusion, administer oral corticosteroids (prednisone or prednisolone) as recommended in Table 2.

Table 2. Recommended Corticosteroid Regimen Starting 1 Day Prior to FAYUVI Administration:

Management of Corticosteroid Regimen:

• Monitor ALT, AST, GGT, and total bilirubin levels closely during corticosteroid therapy [see Dosage and Administration (2.3)]. If liver enzymes are rising or remain elevated above baseline, the corticosteroid dose may be increased or prolonged. Taper corticosteroids after 8 weeks if liver enzymes are at or below baseline. If elevated liver enzymes persist despite the use of corticosteroids, promptly consult a pediatric gastroenterologist or hepatologist and/or immunologist to discuss additional immunosuppression.
• Monitor for and manage adverse reactions secondary to corticosteroid use. Refer to the corticosteroid prescribing information for risks and required precautions.

2.2 Preparation

Required Equipment and Materials:

• Flow rate-controlled syringe pump (prepare the syringe pump prior to administration).
• 20 mL or 50 mL polypropylene syringes for FAYUVI administration (prepare syringes prior to
  • The number and size of syringes will depend on the patient's dose volume.
• 21-gauge stainless steel needles.
• 0.2 micrometer (μm) in-line infusion filter with maximum operating pressure adequate for the syringe pump or pump settings.
• Sterile syringe of Lactated Ringer's solution, Hartmann's solution, or 0.9% sodium chloride injection for flushing the infusion line.

General Precautions:

• Prepare FAYUVI using aseptic technique. Wear gloves and safety glasses during preparation and administration.
• Keep vials away from direct sunlight and in carton packaging prior to use.
• Treat spills of FAYUVI with a virucidal agent with proven activity against non-enveloped viruses and blot using absorbent materials.
• Dispose of unused medicinal product and materials that may have come in contact with FAYUVI in accordance with the local biosafety guidelines.

Thaw and Inspect:

1. Verify the required dose of FAYUVI based on patient's body weight, and confirm the kit contains a sufficient number of vials to prepare FAYUVI infusion for the patient.

2. Do not thaw or puncture vials until immediately prior to use. If the patient is not expected to be ready for same-day administration, store FAYUVI in a manner consistent with How Supplied/Storage and Handling (16).

3. Remove vials from the original packaging. Inspect vials for damage to the vial or cap. Do not use if damaged.

4. Allow vials to thaw at room temperature 20°C – 25°C (68°F – 77°F) for a minimum of 30 minutes until there is no visible ice. Do not use a water bath or external heat sources. Do not shake the vials to avoid foaming. Do not thaw overnight.

5. Visually inspect the thawed vials. FAYUVI is a clear to translucent, colorless liquid that may contain small white to off-white particles. Do not use the vial if the solution is discolored or contains matter other than small white to off-white particles.

Extraction into Syringes:

6. Once thawed, withdraw FAYUVI from the vials into polypropylene syringes using 21-gauge stainless steel needles.

7. Multiple syringes may be needed. Prepare all syringes prior to administering FAYUVI. The contents of multiple vials may be combined into a single syringe.

Addition of In-line Filter and Priming the Infusion System:

8. Insert a 0.2 micrometer (μm) in-line filter between the syringe with FAYUVI and tubing.

9. Prime tubing and filter with FAYUVI.

10. Maintain syringes at room temperature prior to and during administration. FAYUVI is stable for up to 24 hours at room temperature 20°C – 25°C (68°F – 77°F)

2.3 Administration

1. Administer FAYUVI in a setting where personnel and equipment are immediately available to treat severe infusion and hypersensitivity reactions [see Warnings and Precautions (5.4)].

• Insertion of a second intravenous catheter is recommended to treat infusion reactions.

2. Administer FAYUVI as a single-dose slow infusion over approximately 1 hour, through a peripheral vein using an intravenous catheter with a 0.2 micrometer (μm) in-line filter and a syringe pump.

• Do not administer FAYUVI as an intravenous push or bolus.
• Do not infuse FAYUVI in the same intravenous line with any other products.
• Do not use a central line or port.

3. In the event of a severe infusion or hypersensitivity reaction, pause the infusion, and administer supportive care and medical treatment as appropriate. If the infusion is paused, the infusion may be restarted at a slower rate after symptoms are resolved, at the discretion of the treating healthcare provider [see Warnings and Precautions (5.4)].

4. To ensure the patient receives the complete dose, after the content of the last FAYUVI-containing syringe is infused, infuse Lactated Ringer's solution, Hartmann's solution, or 0.9% sodium chloride injection at the same rate that was used for the last part of the infusion to clear FAYUVI from the tubing.

Monitoring Post-Infusion:

Conduct the following tests after FAYUVI administration [see Warnings and Precautions (5.1, 5.2)]:

• ALT, AST, GGT, and total bilirubin levels once weekly during the first 2 weeks, then every 2 weeks until 2 weeks after the corticosteroid taper is complete and as clinically indicated. Continue to monitor liver function in all patients who develop elevated liver enzymes until levels return to baseline.
• Platelet counts weekly for the first 4 weeks, then monthly for 6 months following infusion. Continue monitoring as clinically indicated.

• FAYUVI is shipped and stored frozen at ≤ -60°C [-76°F].
• Store upright at ≤ -60°C [-76°F].
• Store in the original carton until ready to use.
• Thawed vials should not be punctured until immediately prior to use. Once drawn from the vial and prepared in syringes, FAYUVI can be stored at room temperature (20°C – 25°C [68°F – 77°F]) for up to 24 hours, including time for infusion.
• If necessary, an intact vial (stopper not yet punctured) that has been thawed can be stored refrigerated (2°C – 8°C [36°F – 46°F]) for up to 12 days, upright and protected from light (e.g., in the original carton).
• Once thawed, do not refreeze FAYUVI solution vials.
• Follow local guidelines on handling of biological waste.