Two patients with spinal muscular atrophy (SMA) have died following onasemnogene abeparvovec-xioi (Zolgensma®) infusions as a result of acute liver failure. 

Novartis Gene Therapies, the makers of onasemnogene abeparvovec, said in a statement emailed to Rare Disease Advisor that acute liver failure is a known side effect of onasemnogene abeparvovec and is included in the label of the drug. They added that they “firmly believe in the overall favorable risk/benefit profile of Zolgensma.” 

The company has notified all health authorities in countries using onasemnogene abeparvovec, including the US Food and Drug Administration (FDA), and said they will be updating the label of the drug to include the occurrence of fatal acute liver failure.

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The deaths occurred in Russia and Kazakstan around 5 to 6 weeks after infusion with onasemnogene abeparvovec and around 1 to 10 days after corticosteroid taper was started.

Onasemnogene abeparvovec is a disease-modifying treatment for SMA that has been approved by the FDA and in 41 other countries including Japan and Canada. It is also conditionally approved in many European countries. 

Read more about onasemnogene abeparvovec

It is a gene therapy indicated for all types of SMA in patients under the age of 2 years. It consists of an adeno-associated virus serotype 9 (AAV9) vector that carries a fully functional copy of the human SMN gene. It is given to patients as a single intravenous infusion to allow motor neurons to produce their own SMN protein to stop their degeneration and the subsequent degeneration of muscle cells.

To date, onasemnogene abeparvovec has been used to treat more than 2300 people with SMA across the world in clinical trials, managed access programs, and commercially, according to Novartis Gene Therapies.

SMA is caused by biallelic mutations in the SMN1 gene, which encodes almost all of the functional SMN protein in the body.