Zolgensma Label to Include Warning of Acute Liver Failure Deaths
2 treated SMA patients die after acute liver failure following gene therapy's use
Prescribing information for Zolgensma (onasemnogene abeparvovec-xioi), an approved gene therapy for spinal muscular atrophy (SMA), is being updated following the death of two patients who developed acute liver failure after treatment.
Acute liver failure was known to be a potential severe side effect of Zolgensma, highlighted in a boxed warning added in 2021 to on the prescribing information that accompanied its 2019 approval in the U.S. That warning highlighted the risk of higher-than-normal levels of liver enzymes, called aminotransferases, that are suggestive of liver injury, acute liver damage, and acute liver failure.
Zolgensma’s label is now being updated to note that fatal cases of acute liver failure have been reported in treated patients.
Acute liver injury ‘known’ risk of Zolgensma’s use
“While this is clinically important safety information, it is not a new safety signal and we firmly believe in the overall favorable risk/benefit profile of Zolgensma, which to date has been used to treat more than 2,300 patients worldwide across clinical trials, managed access programs, and in the commercial setting,” the company stated.
Novartis reported that it has notified health authorities about these events in all markets where Zolgensma is used. The company is also communicating with relevant healthcare professionals “as an additional step in markets where this action is supported by health authorities,” it added.
SMA is caused by mutations in the gene SMN1, resulting in the dysfunction and death of motor neurons, the nerve cells that control movement. Zolgensma is a one-time therapy administered directly into the bloodstream that uses an engineered viral vector to deliver a working copy of the SMN1 gene to a patient’s cells.
Zolgensma, the first gene therapy for SMA, is widely approved, and it is the second disease-modifying SMA treatment to be approved in the U.S.
Zolgensma is currently approved in the U.S. for newborns and toddlers up to age 2 with all types of SMA. The therapy is also available to treat certain people with SMA in more than 40 other countries, including Canada, Australia, Brazil, Japan, South Korea, Switzerland, and much of the European Union.
Data from the Phase 3 SPRINT (NCT03505099) clinical trial, which tested Zolgensma in babies with SMA treated before the onset of symptoms, were published earlier this year. All of the children in the study were alive at the latest follow-up, and most of these presymptomatic infants hit motor milestones like standing and walking, often within developmentally normal timelines.
Further information on the two SMA patients who died following acute liver failure after treatment with Zolgensma was not available.