Onasemnogene Abeparvovec

Onasemnogene abeparvovec is a recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human SMN protein. SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression.

• 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 )] .

• None. None.contraindicated

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.

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. ( 5.2 ) Thrombocytopenia: Monitor platelet counts before ZOLGENSMA infusion, and at least weekly for the first month and then every other week for the second and third month or until platelet counts return to baseline. ( 2.3 , 5.3 ) Thrombotic Microangiopathy (TMA): Prompt attention to signs and symptoms of TMA is advised, as TMA can result in life-threatening or fatal outcomes. If clinical signs, symptoms and/or laboratory findings occur, consult a pediatric hematologist and/or pediatric nephrologist immediately to manage as clinically indicated. ( 5.4 ) Elevated Troponin I: Increases in cardiac troponin I levels have occurred following ZOLGENSMA infusion. Consider cardiac evaluation after ZOLGENSMA infusion and consult a cardiologist as needed. ( 5.5 ) AAV Vector Integration and Risk of Tumorigenicity: There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome. Report cases of tumors in patients who received ZOLGENSMA, to Novartis Gene Therapies, Inc. ( 5.6 , 17 ) Infusion-Related Reactions: Monitor patients during and after ZOLGENSMA infusion. Interrupt ZOLGENSMA infusion if infusion-related reaction occurs and administer supportive treatment as appropriate. Infusion of ZOLGENSMA may be resumed based on clinical assessment.

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.

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 ) 8.1 Pregnancy Risk Summary There are no available data regarding ZOLGENSMA use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with ZOLGENSMA. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.2 Lactation Risk Summary There is no information available on the presence of ZOLGENSMA in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOLGENSMA and any potential adverse effects on the breastfed child from ZOLGENSMA or from the underlying maternal condition. There is no information on whether breastfeeding should be restricted in mothers who may be seropositive for anti-AAV9 antibodies. 8.4 Pediatric Use The safety of ZOLGENSMA was studied in pediatric patients who received ZOLGENSMA infusion at age 0.3 to 7.9 months (weight range, 3.0 kg to 8.4 kg).

Metabolism

Vector shedding after infusion with onasemnogene abeparvovec was investigated at multiple time points during Study 2. Samples of saliva, urine and stool were collected the day after infusion, weekly through Day 30, and then monthly through Month 12 and every 3 months thereafter.

1. 1Pyrexia53124%
2. 2Vomiting49722%
3. 3Aspartate Aminotransferase Increased34616%
4. 4Alanine Aminotransferase Increased31014%
5. 5Hepatic Enzyme Increased26412%
6. 6Thrombocytopenia1938.7%
7. 7Platelet Count Decreased1677.5%
8. 8Liver Function Test Increased1456.5%
9. 9Pneumonia1376.1%
10. 10Troponin I Increased1305.8%
11. 11Decreased Appetite1215.4%
12. 12Dyspnoea1115.0%
13. 13Cough1084.8%
14. 14Troponin Increased1034.6%
15. 15Transaminases Increased984.4%

The 10 most recently updated of 18 ClinicalTrials.gov registrations naming Onasemnogene Abeparvovec as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec
  Not yet recruiting · Phase 3 · Interventional · 42 enrolled · Biogen
  NCT07444450updated 2026-06-05
• ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)
  Not yet recruiting · Phase 4 · Interventional · 36 enrolled · Novartis Pharmaceuticals
  NCT07448610updated 2026-05-29
• A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy
  Recruiting · Phase 2 · Interventional · 52 enrolled · Scholar Rock, Inc.
  NCT07047144updated 2026-05-01
• Characterization of New Phenotypes of Patients With Spinal Muscular Atrophy Treated With SMN Restoring Therapy
  Recruiting · Interventional · 60 enrolled · Hospices Civils de Lyon
  NCT06321965updated 2026-01-30
• A Study of Dosing Patterns and Costs in Patients With Spinal Muscular Atrophy Receiving Disease Modifying Therapies
  Completed · Observational · 4,114 enrolled · Novartis Pharmaceuticals
  NCT07378943updated 2026-01-30
• Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy
  Terminated · Phase 1 · Interventional · 32 enrolled · Novartis Gene Therapies
  NCT03381729updated 2026-01-26
• Single-Dose Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1
  Completed · Phase 3 · Interventional · 33 enrolled · Novartis Gene Therapies
  NCT03461289updated 2026-01-26
• Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2
  Completed · Phase 3 · Interventional · 30 enrolled · Novartis Gene Therapies
  NCT03505099updated 2026-01-26
• Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
  Completed · Phase 3 · Interventional · 2 enrolled · Novartis Gene Therapies
  NCT03837184updated 2026-01-26
• Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1
  Completed · Phase 3 · Interventional · 22 enrolled · Novartis Gene Therapies
  NCT03306277updated 2026-01-26

Frequently asked questions

How does Onasemnogene Abeparvovec work?

Onasemnogene abeparvovec is a recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human SMN protein. SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression.

What is Onasemnogene Abeparvovec used for?

According to FDA labeling, Onasemnogene Abeparvovec carries indications including: 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 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Onasemnogene Abeparvovec?

Onasemnogene Abeparvovec is classified as Other drugs for disorders of the musculo-skeletal system, Gene Transduction or Replacement, Increased Protein Synthesis.

What are the brand names for Onasemnogene Abeparvovec?

Onasemnogene Abeparvovec is marketed under brand names including Itvisma, Zolgensma.

What are the contraindications for Onasemnogene Abeparvovec?

Onasemnogene Abeparvovec labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.