Zolgensma®: significant uncommon adverse events to be aware of and monitor

Zolgensma® (onasemnogene abeparvovec) is the first gene therapy product to obtain marketing authorization in 2019 in a neuromuscular disease, namely SMA. 

While the beneficial effects of Zolgensma® on motor development are rapid and lasting, serious side effects affecting other organs or tissues have recently been published. 

Analyzes of data from two series totalling over 300 patients with SMA treated with Zolgensma® reveal: 

  • a risk of hepatotoxicity, resulting in particular in an asymptomatic transient rise in transaminases in 90% of people treated, 
  • two cases of severe hepatic failure that occurred resolved on corticosteroids, 
  • at least three cases of thrombotic microangiopathy.

The authors of these articles confirm the value of prophylactic treatment with corticosteroids in reducing this hepatotoxicity, the elimination of all hepatotoxic substances and monitoring of the platelet count. In thrombotic microangiopathy, treatment of thrombocytopenia and renal impairment is symptomatic; it may call for plasma exchanges, dialysis, or even eculizumab-type monoclonal antibodies in the most severe cases. 


Subacute Liver Failure Following Gene Replacement Therapy for Spinal Muscular Atrophy Type I. AG Feldman, JA Parsons, CM Dutmer et al. J Pediatr., 2020 (Mai).


Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy. D Chand, F Mohr, H McMillan et al. J Hepatol., 2020 (Nov). S0168-8278(20)33748-X.


Thrombotic Microangiopathy Following Onasemnogene Abeparvovec for Spinal Muscular Atrophy: A Case Series. D H Chand, C Zaidman, K Arya et al. J Pediatr., 2020 (Nov). S0022-3476(20)31466-9.