GENGLYCOS Suspension for intravenous infusion Ref.[116921] Active ingredients: Pariglasgene brecaparvovec

2.1. Patient Selection

• Select patients without detectable anti-AAV8 antibodies for treatment with GENGLYCOS. Do not administer GENGLYCOS to patients with a detected result for antibodies to AAV8. An FDA authorized test for detection of anti-AAV8 total binding antibodies is not currently available. For information regarding anti-AAV8 antibody testing, contact Ultragenyx Pharmaceutical Inc. at 1-888-756-8657. Currently available tests may vary in accuracy and design.
• Assess adrenal function (perform clinical examination and laboratory testing including morning serum cortisol and ACTH) prior to GENGLYCOS administration [Warnings and Precautions (5.3).
• Assess liver function [perform clinical examination and laboratory testing including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin)] prior to administration [see Warnings and Precautions (5.2)].

2.2. Dose

For single-dose intravenous infusion only The recommended dose of GENGLYCOS is 1.0 × 10¹³ genome copies per kilogram (gc/kg) body weight, administered as a single intravenous infusion.

Table 1. Recommended Dosing:

^a Dose volume is rounded up or down to the nearest 2 mL.
^b Patients weighing >87 kg should be dosed at the 87 kg weight.

2.3. Preparation

General Precautions

• Dilute and prepare GENGLYCOS for intravenous infusion using aseptic technique.
• Verify the required dose of GENGLYCOS based on patient's body weight, and confirm the kit contains enough vials to prepare the GENGLYCOS infusion for the patient.
• Vials should not be thawed or punctured until immediately prior to use. If the patient is not expected to be ready for same-day administration, store GENGLYCOS in a manner consistent with How Supplied/Storage and Handling (16).

Thaw and Inspect:

1. Remove and thaw vials at room temperature 20°C to 25°C (68°F to 77°F) for no more than 30 minutes.

2. Once thawed, gently swirl the vials for 5 to 10 seconds to ensure even mixing. Do not shake. Do not refreeze.

3. Visually inspect the thawed vials. GENGLYCOS is a clear to translucent suspension 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.

Preparation of Solution for Infusion:

4. Withdraw 2 mL of GENGLYCOS from each vial using a polypropylene syringe and 18-gauge needle. Discard any unused portion left in the vials.

• For doses requiring multiple vials, change needles at least every third vial.

5. Remove and discard volume of 0.9% sodium chloride from either the 100 mL infusion bag (for patients weighing 15–39 kg) or 250 mL infusion bag (for patients weighing ≥40 kg) equal to the amount of GENGLYCOS that will be added to the bag. Use a polyvinyl chloride or polypropylene/polyethylene infusion bag. The volume to be withdrawn will vary based on the patient's body weight.

6. Add the contents of the syringes through a sterile 0.2 μm PES or equivalent syringe filter into the infusion bags to bring the volume back up to either 100 mL (for patients weighing 15–39 kg) or 250 mL (for patients weighing ≥ 40 kg). Do not add GENGLYCOS into the airspace of the infusion bag to avoid foaming.

7. Gently invert the infusion bag 4 times to ensure adequate mixing. Do not shake the infusion bag to avoid foaming.

8. Connect the infusion bag to the infusion set equipped with a 0.2-micron(μm) filter and prime the tubing with diluted GENGLYCOS solution up to the hub of the catheter.

9. Diluted GENGLYCOS solution should be administered immediately. If not used immediately, store the diluted solution:

• At room temperature (20°C to 25°C [68°F to 77°F]) for up to 24 hours, including infusion time.
• Refrigerate (2ºC to 8ºC [36ºF to 46 ºF]) and administer within 48 hours, from time of dilution to end of infusion.

Do not freeze the solution.

2.4. Administration

Premedication

Premedicate with acetaminophen and non-sedating antihistamines 30 to 60 minutes prior to infusion of GENGLYCOS.

Administration

1. Administer GENGLYCOS as a single-dose intravenous infusion through a peripheral venous catheter.

2. Do not administer GENGLYCOS as an intravenous push or bolus.

3. Follow the recommended intervals and rates of infusion as shown in Table 2 to minimize the risk for infusion reactions.

Table 2. Recommended Infusion Rates for GENGLYCOS:

^a Ensure all contents of the infusion bag are infused, even if the infusion time exceeds 180 minutes, and is within 24 hours of dose preparation.

4. In the event of an anaphylactic reaction/infusion reaction [see Warnings and Precautions (5.1)], pause the infusion and administer supportive care as clinically indicated to manage the anaphylactic reaction/infusion reaction. If the infusion is paused, restart at half the prior rate after the infusion reaction has resolved. If the infusion needs to be paused and restarted, GENGLYCOS infusion should be completed within 24 hours of dose preparation.

5. After all contents of the bag are infused, flush the tubing with 50 mL of 0.9% sodium chloride (NaCl) injection using the same infusion rate that was used for the last part of the infusion to ensure all GENGLYCOS is delivered. Do not flush the tubing with sodium chloride injection as a bolus.

6. Dispose unused GENGLYCOS and disposable materials that may have come in contact with GENGLYCOS in accordance with the local biosafety guidelines.

Immunosuppressive Therapy

Table 3 includes the recommended corticosteroid regimen starting 2 weeks after GENGLYCOS administration.

Table 3. Recommended Corticosteroid Regimen Starting 2 Weeks after GENGLYCOS Administration:

Monitoring Post-Administration

• Assess liver function (AST, ALT, total bilirubin) after GENGLYCOS administration weekly until 2 weeks after completion of the corticosteroid taper period (see Table 3). If the patient is clinically stable with unremarkable findings (normal clinical exam, total bilirubin, and ALT and AST levels (below 1.5 x ULN or below 1.5 x baseline)) at the end of the corticosteroid taper period, continue to monitor liver function every 2 to 4 weeks until month 6, and as clinically indicated.
  • If hepatic enzyme (ALT or AST) elevations (≥1.5 x ULN and ≥1.5 x baseline) occur, the corticosteroid regimen may need to be initiated or adjusted followed by gradual taper as clinically indicated [see Warnings and Precautions (5.2)].
  • If hepatic enzyme elevations do not respond to corticosteroid adjustment, consult a gastroenterologist or hepatologist.
• Assess adrenal function with morning serum cortisol and ACTH before the corticosteroid regimen, closely monitor adrenal function after GENGLYCOS administration, and repeat testing as clinically indicated. Consult with an endocrinologist in patients with abnormal baseline or persistent low morning cortisol levels. If adrenal insufficiency is suspected, increase the corticosteroid dose to the last tolerated dose and consult an endocrinologist. [see Warnings and Precautions (5.3)].

• GENGLYCOS is shipped and stored at ≤ -60ºC (-76ºF).
• Store upright at ≤ -60ºC (-76ºF).
• Store in the original carton until ready to use.
• Protect GENGLYCOS from light.
• Once thawed, Do not refreeze.
• Vials should not be thawed or punctured until immediately prior to use.
• 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).

After dilution:

• If the diluted GENGLYCOS solution is not administered immediately, it may be stored:
  • at room temperature 20°C to 25°C (68°F to 77°F) for a maximum of 24 hours,

including preparation and infusion times [see Dosage and Administration (2.3, 2.4)], or
** under refrigeration 2°C to 8°C (36°F to 46°F) for up to 48 hours, including preparation and infusion times.
* In case of spills of GENGLYCOS, work surfaces should be decontaminated, and materials should be removed according to local guidelines.

Follow local guidelines on handling and disposal of biological waste.