Zolgensma Dosage/Direction for Use

Treatment should be initiated and administered in clinical centres and supervised by a physician experienced in the management of patients with SMA.
Before administration of onasemnogene abeparvovec, baseline laboratory testing is required, including, but not limited to: AAV9 antibody testing (using an appropriately validated assay), liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin, prothrombin time, partial thromboplastin time (PTT), and international normalised ratio (INR)], creatinine, complete blood count (including haemoglobin and platelet count), and troponin-I.
The need for close monitoring of liver function, platelet count and troponin-I after administration and the need for corticosteroid treatment are to be considered when establishing the timing of onasemnogene abeparvovec treatment (see Precautions).
Due to the increased risk of serious systemic immune response, it is recommended that patients are clinically stable in their overall health status (e.g. hydration and nutritional status, absence of infection) prior to onasemnogene abeparvovec infusion. In case of acute or chronic uncontrolled active infections, treatment should be postponed until the infection has resolved and the patient is clinically stable (see Immunomodulatory regimen as follows and Systemic immune response under Precautions).
Posology: For single-dose intravenous infusion only.
Patients will receive a dose of nominal 1.1 x 10¹⁴ vg/kg onasemnogene abeparvovec. The total volume is determined by patient body weight.
Table 4 gives the recommended dosing for patients who weigh 2.6 kg to 21.0 kg. (See Table 4.)

Click on icon to see table/diagram/image

Immunomodulatory regimen: An immune response to the AAV9 capsid will occur after administration of onasemnogene abeparvovec (see Precautions). This can lead to elevations in liver aminotransferases, elevations of troponin I, or decreased platelet counts (see Precautions and Adverse Reactions). To dampen the immune response immunomodulation with corticosteroids is recommended. Where feasible, the patient's vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion (see Interactions).
Prior to initiation of the immunomodulatory regimen and prior to administration of onasemnogene abeparvovec, the patient must be checked for signs and symptoms of active infectious disease of any nature.
Starting 24 hours prior to infusion of onasemnogene abeparvovec it is recommended to initiate an immunomodulatory regimen following the schedule as follows (see Table 5). If at any time patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone, based on the patient's clinical course, prompt consultation with a paediatric gastroenterologist or hepatologist and adjustment to the recommended immunomodulatory regimen, including increased dose, longer duration or prolongation of corticosteroid taper, should be considered (see Precautions). If oral corticosteroid therapy is not tolerated intravenous corticosteroid may be considered as clinically indicated.

Click on icon to see table/diagram/image

Liver function (ALT, AST, total bilirubin) should be monitored at regular intervals for at least 3 months following onasemnogene abeparvovec infusion (weekly in the first month and during the entire corticosteroid taper period, followed by every two weeks for another month), and at other times as clinically indicated. Patients with worsening liver function test results and/or signs or symptoms of acute illness should be promptly clinically assessed and monitored closely (see Precautions).
If another corticosteroid is used by the physician in place of prednisolone, similar considerations and approach to taper the dose after 30 days should be taken as appropriate.
Special populations: Renal impairment: The safety and efficacy of onasemnogene abeparvovec have not been established in patients with renal impairment and onasemnogene abeparvovec therapy should be carefully considered. A dose adjustment should not be considered.
Hepatic impairment: Patients with ALT, AST, total bilirubin levels (except due to neonatal jaundice) >2 x ULN or positive serology for hepatitis B or hepatitis C have not been studied in clinical studies with onasemnogene abeparvovec. Onasemnogene abeparvovec therapy should be carefully considered in patients with hepatic impairment (see Precautions and Adverse Reactions). A dose adjustment should not be considered.
0SMN1/1SMN2 genotype: No dose adjustment should be considered in patients with a bi-allelic mutation of the SMN1 gene and only one copy of SMN2 (see Pharmacology: Pharmacodynamics under Actions).
Anti-AAV9 antibodies: No dose adjustment should be considered in patients with baseline anti-AAV9 antibody titres above 1:50 (see Precautions).
Paediatric population: The safety and efficacy of onasemnogene abeparvovec in premature neonates before reaching full-term gestational age have not been established. No data are available. Administration of onasemnogene abeparvovec should be carefully considered because concomitant treatment with corticosteroids may adversely affect neurological development.
There is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. Currently available data are described in Pharmacology: Pharmacodynamics under Actions. A dose adjustment should not be considered (see Table 4).
Method of administration: For intravenous use.
Onasemnogene abeparvovec is administered as a single-dose intravenous infusion. It should be administered with a syringe pump as a single intravenous infusion with a slow infusion of approximately 60 minutes. It must not be administered as an intravenous push or bolus.
Insertion of a secondary ('back-up') catheter is recommended in case of blockage in the primary catheter. Following completion of infusion, the line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection.
Precautions to be taken before handling or administering the medicinal product: This medicinal product contains a genetically-modified organism. Healthcare professionals should therefore take appropriate precautions (use of gloves, safety goggles, laboratory coat and sleeves) when handling or administering the product (see Special precautions for disposal and other handling under Cautions for Usage).
For detailed instructions on the preparation, handling, accidental exposure and disposal (including proper handling of bodily waste) of onasemnogene abeparvovec, see Special precautions for disposal and other handling under Cautions for Usage.