Safety profile demonstrated in 4 open-label clinical studies1,a
44 patients were treated with ZOLGENSMA and ranged in age from 0.3 to 7.9 months at the time of infusion1
a4 open-label studies conducted in the United States, including 1 completed clinical trial, 2 ongoing clinical trials, and 1 ongoing, observational, long-term follow-up study of the completed trial.
Adverse reactions occurring in ≥5% of patients following treatment with ZOLGENSMA (N=44)1
ULN=upper limit of normal
aElevated aminotransferases include elevation of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST).
bIn the completed clinical trial, one patient (the first patient infused in that study) was enrolled prior to the protocol amendment instituting administration of prednisolone before and after ZOLGENSMA infusion.
In clinical trials, clinically asymptomatic, transient, elevated aminotransferases were the most common treatment-related adverse reactions and were resolved with a systemic corticosteroid regimen without clinical sequelae.1
- 4.5% (2/44) of patients had ALT and AST elevations of up to 48 x upper limit of normal
- Patients were otherwise asymptomatic, with normal bilirubin
Acute serious liver injury can occur with ZOLGENSMA. Prior to ZOLGENSMA infusion, a patient with infantile-onset SMA had elevated AST and ALT of unknown etiology (gammaglutamyl transferase (GGT), total bilirubin and prothrombin time were normal). The patient was treated under an expanded access program in the United States. The patient received corticosteroids equivalent to oral prednisolone at 1 mg/kg/day for approximately 30 days, followed by a 14-day taper. Approximately 7 weeks after receiving ZOLGENSMA, the patient became jaundiced. Laboratory testing was consistent with acute serious liver injury, with AST level approximately 80 × ULN and ALT level approximately 45 × ULN, total bilirubin approximately 4 × ULN, and plasma prothrombin time approximately 4 × ULN. Liver biopsy showed acute, massive degeneration of hepatocytes, and massive, mixed inflammatory infiltrate (primarily CD8-positive T lymphocytes). The patient recovered to baseline status after treatment with corticosteroids.1
In order to help manage a possible increase in liver aminotransferases, all patients should be treated with systemic corticosteroids before and after infusion. See Full Prescribing Information for important treatment steps including 28-day corticosteroid taper, laboratory testing, and monitoring.
Test for anti-AAV9 antibodies prior to treatment with ZOLGENSMA
- The safety and efficacy of ZOLGENSMA in patients with anti-AAV9 antibody titers above 1:50 have not been evaluated1
- Retesting may be performed if anti-AAV9 antibody titers are reported as positive or elevated1
Prior exposure to AAV9 is rare in the pediatric population1,2
In 2 US clinical trials, 2.4% (1/41) of patients screened were excluded for persistently elevated anti-AAV9 antibody titers.2,a
- Confirmation of anti-AAV9 antibody titers ≤1:50 was required prior to infusion1
aSummary of patients who were screened in US clinical trials and excluded due to persistently elevated anti-AAV9 antibody titers: 1/16 in START; 0/25 in STR1VE.
Temporary vector shedding of ZOLGENSMA may occur, primarily through bodily waste. Advise caregivers on the proper handling and disposal of patient stools. Instructions should be provided to patient families and caregivers regarding good hand hygiene when coming into direct contact with patient bodily waste for up to 1 month after ZOLGENSMA infusion. Disposable diapers should be sealed in disposable trash bags and then discarded into regular trash.1