FDA Approves Zolgensma (onasemnogene abeparvovec-xioi) Gene Therapy to Treat Pediatric Patients with Spinal Muscular Atrophy
BOXED WARNING(WHAT IS THIS?)
WARNING: ACUTE SERIOUS LIVER INJURY
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Acute serious liver injury and elevated aminotransferases can occur with ZOLGENSMA. ( 5.1)
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Patients with pre-existing liver impairment may be at higher risk. ( 8.6)
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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).
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ZOLGENSMA safely and effectively. See full prescribing information for ZOLGENSMA.
ZOLGENSMA� (onasemnogene abeparvovec-xioi)
Suspension for intravenous infusion
Initial U.S. Approval: 2019
WARNING: ACUTE SERIOUS LIVER INJURY SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING.
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Acute serious liver injury and elevated aminotransferases can occur with ZOLGENSMA. (5.1)
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Patients with pre-existing liver impairment may be at higher risk. (8.6)
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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).
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. (1)
Limitation of Use:
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The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated. ( 1, 6.2)
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The use of ZOLGENSMA in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator dependence) has not been evaluated. ( 1, 14)
DOSAGE AND ADMINISTRATION
ZOLGENSMA is for single-dose intravenous infusion only (2).
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The recommended dosage of ZOLGENSMA is 1.1 � 10 14 vector genomes (vg) per kg of body weight.
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Administer ZOLGENSMA as an intravenous infusion over 60 minutes. ( 2.1, 2.3)
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Starting one day prior to ZOLGENSMA infusion, administer systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg of body weight per day for a total of 30 days. At the end of the 30-day period of systemic corticosteroid treatment, check liver function by clinical examination and by laboratory testing. For patients with unremarkable findings, taper the corticosteroid dose over the next 28 days. If liver function abnormalities persist, continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until findings become unremarkable, and then taper the corticosteroid dose over the next 28 days. Consult expert(s) if patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone. ( 2.1)
DOSAGE FORMS AND STRENGTHS
ZOLGENSMA is a suspension for intravenous infusion, supplied as single‑use vials. (3)
ZOLGENSMA is provided in a kit containing 2 to 9 vials, as a combination of 2 vial fill volumes (either 5.5 mL or 8.3 mL). All vials have a nominal concentration of 2.0 � 1013 vector genomes (vg) per mL. Each vial of ZOLGENSMA contains an extractable volume of not less than either 5.5 mL or 8.3 mL. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
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Thrombocytopenia: Monitor platelet counts before ZOLGENSMA infusion, and weekly for the first month and then every other week for the second and third month until platelet counts return to baseline. ( 2.3, 5.2)
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Elevated Troponin‑I: Monitor troponin-I before ZOLGENSMA infusion, and weekly for the first month and then monthly for the second and third month until troponin-I level returns to baseline. ( 2.3, 5.3)
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5%) were elevated aminotransferases and vomiting. (6)
To report SUSPECTED ADVERSE REACTIONS, contact AveXis at 1 833-828-3947 or FDA at 1-800-FDA-1088 or WWW.FDA.GOV/MEDWATCH.
USE IN SPECIFIC POPULATIONS
Pediatric use: Use of ZOLGENSMA in premature neonates before reaching full term gestational age is not recommended because concomitant treatment with corticosteroids may adversely affect neurological development. Delay ZOLGENSMA infusion until full-term gestational age is reached. (8.4)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 5/2019