Zolgensma, or onasemnogene abeparvovec, is an adeno-associated virus vector-based gene therapy that was approved by the FDA in May 2019. Given the newness of this therapy, it is important that healthcare providers are educated on specific information regarding the administration of Zolgensma so that they can optimize treatment for each patient.
In addition to the details of when and how to use Zolgensma, a critical consideration is that acute serious liver injury is the major risk associated with the therapy, and this risk may be heightened in those with pre-existing liver conditions. Being aware of this risk and actively monitoring liver function is a vital part of prescribing and administering Zolgensma.
Indications and Contraindications
Zolgensma has been specifically approved for use in pediatric SMA patients who are less than 2 years old and have bi-allelic mutations in the SMN1 gene. It is recommended that Zolgensma be used only when full-term gestational age has been reached because the corticosteroids that are required during the administration of Zolgensma pose neurological risks for a growing fetus.
Because of the substantial immunosuppression caused by the steroid dose required for Zolgensma administration, it is recommended that patients undergo an adjusted vaccination schedule. Specifically, the MMR and varicella vaccines are contraindicated during periods of significant immunosuppression.
There are no available data yet on:
- The impact of repeat administration of Zolgensma
- The use of Zolgensma in patients with advanced SMA
- The use of Zolgensma during pregnancy
- The use of Zolgensma during breastfeeding
Before administration of Zolgensma, the following should be established:
- Liver function. Liver function should be clinically tested with tests for hepatic aminotrasferases (AST), alanine aminiotransferase (ALT), total bilirubin, and prothrombin time. Following Zolgensma infusion, tests should be performed again weekly for one month and then every other week until results are unremarkable.
If results are unremarkable – meaning tha tfindins are below 2 x upper limit of normal (ULN), the corticosteroid dose should be tapered over the subsequent 28 days. However, if results are abnormal, the dose should remain the same until lab results show that liver functioning in normal. At that point, the dose can be tapered over a 28-day period. In the case that the oral prednisolone does not lead to desired results, experts should be consulted.
After Zolgensma infusion has been administered, liver function should continue to be monitored for at least 3 months.
- Platelet counts and troponin-I. They should also be monitored weekly for one month after infusion of Zolgensma. Platelet counts and troponin I should then be monitored every other week and once a month, respectively, until levels return to baseline.
- Baseline levels of anti-AAV9 antibodies. If antibody titers are great than 1:50, retesting can be performed.
The adverse reactions most likely to occur during Zolgensma administration are elevated aminotransferases and vomiting.
Storage and Handling
Zolgensma is provided as a kit that allows for patient customization and is shipped frozen in clear 10 mL vials. Each vial has a nominal concentration of 2.0 x 1013 genomes (vg) per mL. The pre-determined fill volumes supplied are 5.5 mL and 8.3 mL.
The kits contain between 2 and 9 vials of Zolgensma. Each vial also comes with one alcohol wipe.
Below is information provided by the FDA and the Zolgensma package insert on Zolgensma kit sizes.
Once the kit arrives, it should be refrigerated at a temperature between 2℃ and 8℃ (or 36℉ and 46℉). It should not be refrozen. It contains no preservative and must be used within 14 days.
Zolgensma must be thawed before use. The kit can be thawed by:
- Placing it in the refrigerator for approximately 12 hours
- Placing it at room temperature for approximately 4 hours
Once thawed, Zolgensma should look slightly opaque, between colorless and faint white, and contain no particles. It should not be used if it does not visibly fit this description, and it should not be shaken.
Dosing and Timing
Zolgensma is meant to be administered intravenously as a single dose over 60 minutes. It is provided as a sterile suspension, and the recommended dose is 1.1 x 1014 vector genomes (vg) per kilogram (kg) of the patient’s body weight.
Below is information provided by the FDA and the Zolgensma package insert on the specific dose volume (in mL) required based on a patient’s weight (in kg).
Beginning a day before Zolgensma infusion, corticosteroids should be administered at a dose equivalent to an oral predinisolone dose of 1 mg/kg of body weight each day for 30 days.
To administer Zolgensma, a primary catheter should be placed into a vein. A peripheral vein in the arm or leg is recommended, as is insertion of a back-up catheter. The syringe pump should be programmed for saline priming, or the tubing can be primed manually with saline. The Zolgensma should then be infused slowly over 60 minutes, with no infusion as intravenous push or bolus. Once the infusion is complete, the line should be flushed with saline.
1. Al-Zaidy SA, Mendell JR. From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1. Pediatr Neurol. June 2019. doi:10.1016/j.pediatrneurol.2019.06.007
2. Highlights of prescribing information. fda.gov. https://www.fda.gov/media/126109/download. Published 2019. Accessed September 5, 2019.