Zolgensma (onasemnogene abeparvovec-xioi)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved May 2019

Specific Treatments:

pediatrics <2 years of age with spinal muscular atrophy with bi-allelic mutations in the SMN1 gene

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General Information

Zolgensma (onasemnogene abeparvovec-xioi) is an adeno-associated virus vector-based gene therapy.

Zolgensma is specifically 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. 

Zolgensma is supplied as a suspension for intravenous administration. Zolgensma is for single-dose intravenous infusion only. The recommended dosage of Zolgensma is 1.1 × 1014 vector genomes (vg) per kg of body weight. Administer Zolgensma as an intravenous infusion over 60 minutes.

• 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.

Clinical Results

FDA Approval

The FDA approval of Zolgensma was based on the STRIVE and START clinical trials. Efficacy was established based on survival, and achievement of developmental motor milestones such as sitting without support. Survival was defined as time from birth to either death or permanent ventilation. Permanent ventilation was defined as requiring invasive ventilation (tracheostomy), or respiratory assistance for 16 or more hours per day (including noninvasive ventilatory support) continuously for 14 or more days in the absence of an acute reversible illness, excluding perioperative ventilation. Efficacy was also supported by assessments of ventilator use, nutritional support and scores on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). CHOP-INTEND is an assessment of motor skills in patients with infantile-onset SMA. 

STRIVE, an ongoing, open-label, single-arm clinical trial, evaluated Zolgensma in pediatric patients less than 2 years of age with SMA with bi-allelic mutations in the SMN1 gene. Patients experienced onset of clinical symptoms consistent with SMA before 6 months of age. All patients had genetically confirmed bi-allelic SMN1 gene deletions, two copies of the SMN2 gene, and absence of the c.859G>C modification in exon 7 of SMN2 gene (which predicts a milder phenotype). All patients had baseline anti-AAV9 antibody titers of ≤ 1:50, measured by ELISA. In both trials, Zolgensma was delivered as a single-dose intravenous infusion. 

STR1VE has enrolled 21 patients (10 male and 11 female) with infantile-onset SMA. Before treatment with Zolgensma, none of the 21 patients required non-invasive ventilator (NIV) support, and all patients could exclusively feed orally. The mean CHOP-INTEND score at baseline was 31.0 (range 18 to 47). All the patients received 1.1 × 10[1][4] vg/kg of Zolgensma. The mean age of the 21 patients at the time of treatment was 3.9 months (range 0.5 to 5.9 months). As of the March 2019 data cutoff, 19 patients were alive without permanent ventilation (i.e., event-free survival) and were continuing in the trial, while one patient died at age 7.8 months due to disease progression, and one patient withdrew from the study at age 11.9 months. The 19 surviving patients who were continuing in the trial ranged in age from 9.4 to 18.5 months. By the data cutoff, 13 of the 19 patients continuing in the trial reached 14 months of age without permanent ventilation, one of the study's co-primary efficacy endpoints. In addition to survival, assessment of the other co-primary efficacy endpoint found that 10 of the 21 patients (47.6%) achieved the ability to sit without support for >= 30 seconds between 9.2 and 16.9 months of age (mean age was 12.1 months). Based on the natural history of the disease, patients who met the study entry criteria would not be expected to attain the ability to sit without support, and only approximately 25% of these patients would be expected to survive beyond 14 months of age. In addition, 16 of the 19 patients had not required daily NIV use. Comparison of the results of the ongoing clinical trial to available natural history data of patients with infantile-onset SMA provides primary evidence of the effectiveness of Zolgensma.

START enrolled 15 patients (6 male and 9 female) with infantile-onset SMA, 3 in a low-dose cohort and 12 in a high-dose cohort. At the time of treatment, the mean age of patients in the low-dose cohort was 6.3 months (range 5.9 to 7.2 months), and 3.4 months (range 0.9 to 7.9 months) in the high-dose cohort. The dosage received by patients in the low-dose cohort was approximately one-third of the dosage received by patients in the high-dose cohort. By 24 months following Zolgensma infusion, one patient in the low-dose cohort met the endpoint of permanent ventilation; all 12 patients in the high-dose cohort were alive without permanent ventilation. None of the patients in the low-dose cohort were able to sit without support, or to stand or walk; in the high-dose cohort, 9 of the 12 patients (75.0%) were able to sit without support for > 30 seconds, and 2 patients (16.7%) were able to stand and walk without assistance.

Side Effects

Adverse effects associated with the use of Zolgensma may include, but are not limited to, the following:

elevated aminotransferases


The Zolgensma drug label comes with the following Black Box Warning: Acute serious liver injury and elevated aminotransferases can occur with Zolgensma. Patients with pre-existing liver impairment may be at higher risk. 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.


Mechanism of Action

Zolgensma (onasemnogene abeparvovec-xioi) is an adeno-associated virus vector-based gene therapy. This recombinant AAV9-based gene therapy is 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. Intravenous administration of Zolgensma that results in cell transduction and expression of the SMN protein has been observed in two human case studies.

Additional Information

For additional information regarding Zolgensma or spinal muscular atrophy, please visit the Zolgensma page