Boxed Warning
Acute serious liver injury
Acute serious liver injury and elevated aminotransferases can occur with onasemnogene abeparvovec. Patients with preexisting liver impairment may be at higher risk. Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing (eg, hepatic aminotransferases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], total bilirubin, and prothrombin time). Administer systemic corticosteroid to all patients before and after onasemnogene abeparvovec infusion. Continue to monitor liver function for at least 3 months after infusion.
Dosage Forms
Suspension, Injection [preservative free]
Zolgensma: onasemnogene abeparvovec-xioi 20000000000000 VG/mL (5.5 mL, 8.3 mL)
Pharmacology
Mechanism of Action
A recombinant adeno-associated virus vector-based gene therapy that delivers a normal copy of the gene encoding human survival motor neuron (SMN) protein.
Use: Labeled Indications
Spinal muscular atrophy: Treatment of pediatric patients <2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene
Limitations of use: Safety and effectiveness of repeat administration has not been evaluated. Use in patients with advanced SMA (eg, complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Pediatric
Spinal muscular atrophy (SMA): Note: One day prior to infusion, administer oral corticosteroids (eg prednisolone 1 mg/kg/dose once daily or equivalent) and continue for at least 30 days.
Infants and Children <2 years: IV infusion: 1.1 x 1014 vector genomes/kg as a single dose.
Dose volume based on weight range:
|
Weight range (kg) |
Dose Volume (mL) |
|---|---|
|
2.6 to 3 |
16.5 |
|
3.1 to 3.5 |
19.3 |
|
3.6 to 4 |
22 |
|
4.1 to 4.5 |
24.8 |
|
4.6 to 5 |
27.5 |
|
5.1 to 5.5 |
30.3 |
|
5.6 to 6 |
33 |
|
6.1 to 6.5 |
35.8 |
|
6.6 to 7 |
38.5 |
|
7.1 to 7.5 |
41.3 |
|
7.6 to 8 |
44 |
|
8.1 to 8.5 |
46.8 |
|
8.6 to 9 |
49.5 |
|
9.1 to 9.5 |
52.3 |
|
9.6 to 10 |
55 |
|
10.1 to 10.5 |
57.8 |
|
10.6 to 11 |
60.5 |
|
11.1 to 11.5 |
63.3 |
|
11.6 to 12 |
66 |
|
12.1 to 12.5 |
68.8 |
|
12.6 to 13 |
71.5 |
|
13.1 to 13.5 |
74.3 |
|
≥13.6 |
Multiple kits will be required. |
Table has been converted to the following text:
If weight range is 2.6 to 3 kg: Dose volume: 16.5 mL
If weight range is 3.1 to 3.5 kg: Dose volume: 19.3 mL
If weight range is 3.6 to 4 kg: Dose volume: 22 mL
If weight range is 4.1 to 4.5 kg: Dose volume: 24.8 mL
If weight range is 4.6 to 5 kg: Dose volume: 27.5 mL
If weight range is 5.1 to 5.5 kg: Dose volume: 30.3 mL
If weight range is 5.6 to 6 kg: Dose volume: 33 mL
If weight range is 6.1 to 6.5 kg: Dose volume: 35.8 mL
If weight range is 6.6 to 7 kg: Dose volume: 38.5 mL
If weight range is 7.1 to 7.5 kg: Dose volume: 41.3 mL
If weight range is 7.6 to 8 kg: Dose volume: 44 mL
If weight range is 8.1 to 8.5 kg: Dose volume: 46.8 mL
If weight range is 8.6 to 9 kg: Dose volume: 49.5 mL
If weight range is 9.1 to 9.5 kg: Dose volume: 52.3 mL
If weight range is 9.6 to 10 kg: Dose volume: 55 mL
If weight range is 10.1 to 10.5 kg: Dose volume: 57.8 mL
If weight range is 10.6 to 11 kg: Dose volume: 60.5 mL
If weight range is 11.1 to 11.5 kg: Dose volume: 63.3 mL
If weight range is 11.6 to 12 kg: Dose volume: 66 mL
If weight range is 12.1 to 12.5 kg: Dose volume: 68.8 mL
If weight range is 12.6 to 13 kg: Dose volume: 71.5 mL
If weight range is 13.1 to 13.5 kg: Dose volume: 74.3 mL
If weight range is ≥13.6 kg: Dose volume: Multiple kits will be required.
Concomitant therapy: Beginning the day prior to onasemnogene abeparvovec infusion, oral prednisolone (1 mg/kg/day or equivalent) should be administered and continued for ≥30 days to help prevent hepatic toxicity. At the end of 30 days, clinically assess liver and test hepatic function (ALT, AST, total bilirubin, and prothrombin time [PT]); if unremarkable findings (normal clinical exam, total bilirubin, and PT, and ALT and AST concentrations <2 x ULN), taper prednisolone over 28 days. If evidence of hepatic impairment exists, continue oral prednisolone (1 mg/kg/day or equivalent) until AST/ALT <2 x ULN and all other assessments return to normal, then taper over 28 days. If unresponsive to corticosteroid therapy, consult expert.
Storage
Product is shipped and delivered frozen at ≤-60°C (-76°F). Upon receipt, store at 2°C to 8°C (36°F to 46°F) for ≤14 days. Do not refreeze.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%:
Hepatic: Increased serum alanine aminotransferase (≤27%), increased serum aspartate aminotransferase (≤27%)
Immunologic: Antibody development (100%)
1% to 10%: Gastrointestinal: Vomiting (7%)
Frequency not defined:
Hematologic & oncologic: Thrombocytopenia
Miscellaneous: Troponin increased in blood specimen
<1%, postmarketing, and/or case reports: Acute hepatotoxicity, jaundice
Warnings/Precautions
Concerns related to adverse effects:
- Cardiac effects: Transient increases in troponin-I levels have been observed, but clinical significance is unknown; cardiac toxicity was observed in animal studies. Monitor troponin-I prior to initiation of therapy and for ≥3 months after infusion.
- Hepatic effects: [US Boxed Warning]: Acute serious liver injury and elevated serum liver aminotransferases can occur. Use with caution in patients with preexisting liver impairment. Monitor liver function prior to initiation of therapy and for ≥3 months after infusion. Administer a corticosteroid to all patients before and after infusion.
- Thrombocytopenia: Transient decreases in platelet counts have been observed; monitor platelet counts before and after therapy.
Concurrent drug therapy issues:
- Vaccines: Vaccination schedule may need adjusted due to corticosteroid administration before and after onasemnogene abeparvovec infusion.
Other warnings/precautions:
- Immunogenicity: Safety and efficacy has not been evaluated in patients with anti-AAV9 antibody titers above 1:50. Perform baseline testing for the presence of anti-AAV9 antibodies; retesting may be performed if anti-AAV9 antibody titers are reported as >1:50.
- Vector shedding: Temporary vector shedding of onasemnogene abeparvovec occurs primarily through body waste. Recommended procedures when handling patient feces include sealing disposable diapers in disposable trash bags and then discarding into regular trash. Use proper hand hygiene when coming into direct contact with patient body waste. Follow these precautions for one month after the infusion.
Monitoring Parameters
Anti-AAV9 antibody testing at baseline (may re-test if anti-AAV9 antibody titers are reported >1:50)
Liver function: Clinical exam, AST, ALT, total bilirubin, prothrombin time at baseline, weekly for the first month, then every other week for the second and third months; continue testing until results are unremarkable (normal clinical exam, total bilirubin and prothrombin time; AST and ALT levels <2 x ULN).
Platelet count: Baseline, weekly for the first month, then every other week for the second and third months; continue testing until platelet count returns to baseline
Troponin-I: Baseline, weekly for the first month, then monthly for the second and third months; continue testing until troponin-I level returns to baseline
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted. Onasemnogene abeparvovec is not approved for use in patients of reproductive age.
Patient Education
- Discuss specific use of drug and side effects with caregiver as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience vomiting. Have caregiver report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), bruising, bleeding, cough, sneezing, runny nose, or sore throat (HCAHPS).
- Educate caregiver about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Caregiver should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
