Safety risks associated with the use of intravenous onasemnogene abeparvovec for the treatment of spinal muscular atrophy (SMA) include hepatotoxicity, transient thrombocytopenia, cardiac events, thrombotic microangiopathy, and ganglionopathy. This is according to a new study published in Drug Safety that described the overall safety of the treatment based on the results of preclinical and clinical studies and postmarketing data.

John W. Day MD, PhD, and the coauthors of the study wrote, “Risks associated with onasemnogene abeparvovec can be anticipated and monitored with diligent standard of care and sometimes require medical management.”

Onasemnogene abeparvovec is the only systemically administered gene-replacement therapy for SMA approved by the US Food and Drug Administration (FDA). It uses a recombinant adeno-associated virus serotype 9 (AAV9) to deliver a functional copy of the SMN gene to the patient’s body.

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In the present study, researchers performed single-dose toxicity studies in neonatal mice as well as in neonatal and juvenile cynomolgus nonhuman primates. They also presented data from preclinical studies, 7 clinical trials comprising 102 patients, and postmarketing sources.

They reported that they observed inflammation of the dorsal root ganglia in cynomolgus nonhuman primates, which may also affect human patients. 

In clinical trials, all patients except 1 experienced at least 1 treatment-emergent adverse event and 50 of the 102 experienced serious adverse events, 11 of which were considered treatment-related. Prednisolone treatment resolved adverse events consistent with hepatotoxicity. 

The researchers also reported that thrombotic microangiopathy was observed in the postmarketing setting. They stated that patients may require medical intervention for this complication.

The researchers wrote, “Risks associated with onasemnogene abeparvovec can be anticipated, monitored, and managed.”

They cautioned the reader that their data may not be complete since the reporting of postmarketing data is voluntary and includes sources such as social media, published literature, market research, and public databases.


Day JW, Mendell JR, Mercuri E, et al. Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy. Drug Saf. Published online August 12, 2021. doi:10.1007/s40264-021-01107-6