Zolgensma

Zolgensma is an FDA-registered drug product whose active ingredient is ONASEMNOGENE ABEPARVOVEC-XIOI. It is labelled by Novartis Innovative Technologies Inc. and marketed as a human prescription drug product. Identifiers on file: NDC 71894-120, application BLA125694, label effective 20260616. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing ONASEMNOGENE ABEPARVOVEC-XIOI are most often described in connection with: zolgensma adeno-associated, virus aav, vector-based gene, therapy indicated, treatment pediatric, patients less, years age, spinal muscular. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE ZOLGENSMA is an adeno-associated virus (AAV) 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. Limitations 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 )] . ZOLGENSMA is an adeno-associated virus (AAV) 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 ) Limitations of Use The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated. ( 1 , 6.2 ) The use of ZOLGENSMA in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator dependence) has not been evaluated. ( 1 , 14 )

2 DOSAGE AND ADMINISTRATION For single-dose intravenous infusion only. For single-dose intravenous infusion only ( 2 ). The recommended dosage of ZOLGENSMA is 1.1 × 10 14 vector genomes (vg) per kg of body weight. ( 2.1 ) Administer ZOLGENSMA as an intravenous infusion over 60 minutes. ( 2.1 , 2.3 ) Postpone ZOLGENSMA in patients with infections until the infection has resolved and the patient is clinically stable. ( 2.1 , 5.2 ) 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, check liver function by clinical examination and by laboratory testing. For patients with unremarkable findings, taper the corticosteroid dose gradually 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 gradually over the next 28 days or longer if needed. Do not stop systemic corticosteroids abruptly. ( 2.1 ) If liver function abnormalities continue to persist ≥ 2 × ULN after the 30-day period of systemic corticosteroids, promptly consult a pediatric gastroenterologist or hepatologist. ( 2.1 ) 2.1 Dose and Administration The recommended dose of ZOLGENSMA is 1.1 × 10 14 vector genomes per kilogram (vg/kg) of body weight. Table 1: Dosing Patient weight range (kg) Dose volume a (mL) 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 21.0 kg. 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 – 13.5 74.3 13.6 – 14.0 77.0 14.1 – 14.5 79.8 14.6 – 15.0 82.5 15.1 – 15.5 85.3 15.6 – 16.0 88.0 16.1 – 16.5 90.8 16.6 – 17.0 93.5 17.1 – 17.5 96.3 17.6 – 18.0 99.0 18.1 – 18.5 101.8 18.6 – 19.0 104.5 19.1 – 19.5 107.3 19.6 – 20.0 110.0 20.1 – 20.5 112.8 20.6 – 21.0 115.5 Prior to ZOLGENSMA infusion: Due to the increased risk of serious systemic immune response, administer ZOLGENSMA to patients who are clinically stable in their overall baseline health status (e.g., hydration and nutritional status, absence of infection) prior to infusion. Postpone ZOLGENSMA in patients with infections until the infection has resolved and the patient is clinically stable. Clinical signs or symptoms of infection should not be evident at the time of ZOLGENSMA infusion [see Warnings and Precautions ( 5.2 , 5.4 ), Patient Counseling Information ( 17 )]. Assess liver function [see Boxed Warning, Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.6 )]. Obtain creatinine and complete blood count (including hemoglobin and platelet count) [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 , 5.4 )] . Perform baseline testing for the presence of anti-AAV9 antibodies [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.2 )]. One day prior to ZOLGENSMA infusion, begin administration of systemic corticosteroids equivalent to oral prednisolone at 1 mg per kg 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, and at other times as clinically indicated [see Dosage and Administration ( 2.3 )] . At the end of the 30-day period of systemic corticosteroid treatment, check liver status clinically and by assessing alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, prothrombin time, and international normalized ratio (INR). Promptly assess and closely monitor patients with worsening liver function test results and/or signs or symptoms of acute illness (e.g., vomiting, deterioration in health) [see Warnings and Precautions ( 5.1 )] . For patients with unremarkable findings (normal clinical exam, total bilirubin, prothrombin time, and INR and ALT and AST levels below 2 × upper limit of normal [ULN]): Taper the corticosteroid dose gradually over the next 28 days. Do not stop systemic corticosteroids abruptly [see Warnings and Precautions ( 5.1 )] . 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 gradually over the next 28 days or longer if needed. Do not stop systemic corticosteroids abruptly [see Warnings and Precautions ( 5.1 )] . If liver function abnormalities continue to persist ≥ 2 × ULN after the 30-day period of systemic corticosteroids, promptly consult a pediatric gastroenterologist or hepatologist [see Warnings and Precautions ( 5.1 )] . If oral corticosteroid therapy is not tolerated, consider intravenous corticosteroids as clinically indicated [see Warnings and Precautions ( 5.1 )] . 2.2 Preparation Thaw ZOLGENSMA before use. The contents of the ZOLGENSMA kit will thaw in approximately 16 hours if placed in a refrigerator, or in approximately 6 hours if placed at room temperature. If thawed in a refrigerator, remove from refrigerator on day of dosing. When thawed, ZOLGENSMA is a clear to slightly opaque, colorless to faint white liquid, free of particles. Visually inspect vials for particulate matter and discoloration prior to infusion. Do not use vials if particulates or discoloration are present. DO NOT SHAKE. Draw the appropriate dose volume from all vials into a syringe, remove air from the syringe, cap the syringe, and deliver the syringe at room temperature to the patient infusion location. Use ZOLGENSMA within 8 hours of drawing into syringe. Discard the vector-containing syringe if the drug is not infused within the 8-hour timeframe. DO NOT REFREEZE. 2.3 Laboratory Testing and Monitoring to Assess Safety Perform baseline anti-AAV9 antibody testing prior to ZOLGENSMA infusion. Retesting may be performed if anti-AAV9 antibody titers are reported as > 1:50 [see Dosage and Administration ( 2.1 )] . Conduct the following tests at baseline and as directed below [see Warnings and Precautions ( 5.1 , 5.3 , 5.5 )] : Liver function (clinical exam, AST, ALT, total bilirubin, albumin, prothrombin time, partial thromboplastin time [PTT], and INR) at baseline. Monitor liver function (AST, ALT, total bilirubin, prothrombin time, INR) weekly for the first month after ZOLGENSMA infusion and during the corticosteroid taper period (28 days or longer if needed). If the patient is clinically stable with unremarkable findings (normal clinical exam, total bilirubin, and prothrombin and INR results, and ALT and AST levels below 2 × ULN) at the end of the corticosteroid taper period, continue to monitor liver function every other week for another month. Platelet counts weekly for the first month, and then every other week for the second and third months, until platelet counts return to baseline.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 5%) were elevated aminotransferases and vomiting. The most common adverse reactions (incidence ≥ 5%) were elevated aminotransferases and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Gene Therapies at 1-833-828-3947 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to ZOLGENSMA in five clinical studies enrolling a total of 68 patients. This includes four prospective open-label clinical trials [NCT03306277 (Study 1), NCT02122952 (Study 2), NCT03505099, NCT04851873 (Study 3)], and one observational long-term follow-up study [NCT03421977]. The patient population in NCT03306277, NCT03505099, and NCT02122952 ranged in age from 0.3 months to 7.9 months at the time of infusion (median age, 3.3 months), with weight range from 3.0 kg to 8.4 kg (median weight, 5.5 kg) [see Clinical Studies ( 14 )] . In an open-label, post-authorization clinical study (Study 3, NCT04851873), safety of ZOLGENSMA was evaluated in 24 children, aged between 1.5 to 9.1 years (median age, 4.9 years), with weight range from ≥ 8.5 kg to ≤ 21 kg (median weight, 15.8 kg). Only one of the 24 patients was under the age of 2 years at the time of ZOLGENSMA administration. Patients in Study 3 had 2 to 4 copies of SMN2 . Before treatment with ZOLGENSMA, 21 patients discontinued their previous treatment with nusinersen or risdiplam. The types of adverse reactions observed in Study 3 were consistent with those of Studies 1 and 2. Liver enzyme increases in Study 3 occurred at a higher frequency compared with the previous 4 studies. AST or ALT elevations > 2 × ULN were observed in the majority of patients (23 out of 24 patients), including 21 patients with ALT elevations > 3 × ULN and 5 patients with ALT elevations > 20 × ULN. These patients were clinically asymptomatic and there were no elevations of bilirubin. The AST and ALT elevations were managed with the use of corticosteroids, typically with prolonged duration and/or given at a higher dose [see Warnings and Precautions ( 5.1 )] . Transient decreases in platelet counts, which met the criteria for thrombocytopenia were observed in 20 out of 24 patients. Four patients had platelet counts below 50,000 per µL [see Warnings and Precautions ( 5.3 )] . The most frequent adverse reactions (incidence ≥ 5%) and increases in alanine aminotransferase in the 4 studies (data cut-off date: September 27, 2018) are summarized in Table 2 . Table 2: Adverse Reactions and ALT Increases* Following Treatment With ZOLGENSMA Patients n = 44 (3.0-8.4 kg) Adverse reactions n (%) Abbreviations: ULN, upper limit of normal; ALT, alanine aminotransferase. *Laboratory finding. Elevated aminotransferases 12 (27%) ALT > 3 X ULN 7 (16%) ALT > 20 X ULN 4 (9%) Vomiting 3 (7%) One death occurred in a patient, who received ZOLGENSMA at the age of 5 months (6 kg), in a completed non-United States clinical trial (NCT03461289). The patient initially presented with respiratory insufficiency 12 days after ZOLGENSMA infusion and was found to have RSV and parainfluenza in respiratory secretions. The patient had episodes of serious hypotension, followed by seizures, and was found to have leukoencephalopathy (brain white matter defects) approximately 30 days after ZOLGENSMA infusion. The patient died after withdrawal of life support 52 days after ZOLGENSMA infusion. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZOLGENSMA. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : thrombotic microangiopathy [see Warnings and Precautions ( 5.4 )] , thrombocytopenia [see Warnings and Precautions ( 5.3 )] Hepatobiliary Disorders : acute liver failure (fatal and non-fatal), acute liver injury [see Warnings and Precautions ( 5.1 )] General Disorders and Administration Site Conditions : pyrexia, infusion-related reactions [see Warnings and Precautions ( 5.7 )] Investigations : troponin increased [see Warnings and Precautions ( 5.5 )]

What is Zolgensma used for?
1 INDICATIONS AND USAGE ZOLGENSMA is an adeno-associated virus (AAV) 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. Limitations of Use The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated [see Adverse …

Who makes Zolgensma?
Novartis Innovative Technologies Inc. is the labeler of record for Zolgensma.

Is Zolgensma prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has Zolgensma been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.