Zolgensma

ZOLGENSMA- onasemnogene abeparvovec-xioi
AveXis, Inc.

WARNING: ACUTE SERIOUS LIVER INJURY

Acute serious liver injury and elevated aminotransferases can occur with ZOLGENSMA. (5.1)
Patients with pre-existing liver impairment may be at higher risk. (8.6)
Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing (e.g., hepatic aminotransferases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], total bilirubin, and prothrombin time). Administer systemic corticosteroid to all patients before and after ZOLGENSMA infusion. Continue to monitor liver function for at least 3 months after infusion (2.1) (2.3).

1 INDICATIONS AND USAGE

ZOLGENSMA (onasemnogene abeparvovec-xioi) is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

Limitation of Use

The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated [see Adverse Reactions ( 6.2) ].
The use of ZOLGENSMA in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated [see Clinical Studies ( 14) ].

2 DOSAGE AND ADMINISTRATION

For single-dose intravenous infusion only.

2.1 Dose and Administration

The recommended dose of ZOLGENSMA is 1.1 × 1014 vector genomes per kilogram (vg/kg) of body weight.

Table 1: Dosing
Patient Weight Range (kg) Dose Volumea (mL)

2.6 – 3.0

16.5

3.1 – 3.5

19.3

3.6 – 4.0

22.0

4.1 – 4.5

24.8

4.6 – 5.0

27.5

5.1 – 5.5

30.3

5.6 – 6.0

33.0

6.1 – 6.5

35.8

6.6 – 7.0

38.5

7.1 – 7.5

41.3

7.6 – 8.0

44.0

8.1 – 8.5

46.8

8.6 – 9.0

49.5

9.1 – 9.5

52.3

9.6 – 10.0

55.0

10.1 – 10.5

57.8

10.6 – 11.0

60.5

11.1 – 11.5

63.3

11.6 – 12.0

66.0

12.1 – 12.5

68.8

12.6 – 13.0

71.5

13.1 – 13.5b

74.3

a Dose volume is calculated using the upper limit of the patient weight range for pediatric patients less than 2 years of age between 2.6 kg and 13.5 kg

b Dose volume for pediatric patients less than 2 years of age weighing equal to or greater than 13.6 kg will require a combination of ZOLGENSMA kits.

Prior to ZOLGENSMA infusion
o
Assess liver function [see Boxed Warning, Laboratory Testing and Monitoring to Assess Safety (2.3), Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].
o
Measure platelet counts and troponin-I [see Laboratory Testing and Monitoring to Assess Safety (2.3), Warnings and Precautions (5.2)(5.3)]
o
Perform baseline testing for the presence of anti-AAV9 antibodies [see Laboratory Testing and Monitoring to Assess Safety (2.3), Adverse Reactions (6.2)].
One day prior to ZOLGENSMA infusion, begin administration of systemic corticosteroids equivalent to oral prednisolone at 1 milligram per kilogram of body weight per day (mg/kg/day) for a total of 30 days.
Administer ZOLGENSMA as a single‑dose intravenous infusion through a venous catheter.

Follow the steps below for infusion:

1.
Place a primary catheter into a vein (generally a peripheral vein in the arm or leg). Insertion of a back-up catheter is recommended.
2.
Program syringe pump for saline priming, or prime tubing manually with saline.
3.
Administer ZOLGENSMA as a slow infusion over 60 minutes. DO NOT INFUSE AS AN INTRAVENOUS PUSH OR BOLUS.
4.
Flush line with saline following completion of infusion.
Monitor liver function by clinical examination and by laboratory testing on a regular basis [see Laboratory Testing and Monitoring to Assess Safety ( 2.3) ].
o
At the end of the 30-day period of systemic corticosteroid treatment, check liver status clinically and by assessing ALT, AST, total bilirubin, and prothrombin time.
o
For patients with unremarkable findings (normal clinical exam, total bilirubin, and prothrombin time, and ALT and AST levels below 2 × upper limit of normal (ULN)), taper the corticosteroid dose over the next 28 days [see Warnings and Precautions (5.1) ].
o
If liver function abnormalities persist, continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until AST and ALT values are both below 2 × ULN and all other assessments return to normal range, and then taper the corticosteroid dose over the next 28 days.
o
Consult expert(s) if patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone.

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