Warning of Acute Liver Failure Added to Zolgensma Label

Marta Figueiredo PhD avatar

by Marta Figueiredo PhD |

Share this article:

Share article via email
Zolgensma | SMA News Today | liver failure warning | illustration of woman with megaphone

The U.S. Food and Drug Administration (FDA) has added acute liver failure to the list of safety concerns with use of Zolgensma (onasemnogene abeparvovec-xioi) in children with spinal muscular atrophy (SMA).

The therapy’s label has been updated to contain a boxed warning highlighting the risk of higher-than-normal levels of liver enzymes called aminotransferases (suggestive of liver injury), acute liver damage, and acute liver failure.

SMA is caused by mutations in the SMN1 gene that impair the production of SMN, a protein found in virtually every cell in the body. Notably, motor neurons — the specialized nerve cells that control voluntary movement — are particularly sensitive to SMN deficiency, dying as a result and subsequently leading to muscle weakness and wasting.

Novartis Gene Therapies’ Zolgensma is a gene therapy approved for children with SMA up to age 2 in the U.S. and Japan, and to babies and young children up to 21 kg (about 46 pounds) in the European Union and Canada.

Recommended Reading
Main graphic for

My Search for Nursing Care Showed Me What I Can Do

Administered directly into the bloodstream at a dose proportional to a patient’s body weight, it uses a modified and harmless virus to deliver a working copy of SMN1 to cells.

Given that cells that do not divide into new cells (like motor neurons) are less likely to lose the delivered gene over time, a single dose of Zolgensma is expected to promote sustained SMN levels in these highly susceptible cells.

Nevertheless, the therapy can be given only once due to the body’s natural production of immune antibodies against the viral carrier. However, patients still may develop immune reactions after the single dose, which can increase the levels of liver enzymes — an indicator of liver damage — and drop those of platelets.

For that reason, an oral immunosuppressive regimen is started on the day before treatment and continued for 30 days. In addition, liver health and platelet counts are monitored prior to treatment, and at regular periods thereafter for at least three months.

Regarding liver-related adverse events with Zolgensma, the label states that liver toxicity has been generally manifested as elevated levels of liver enzymes, but some cases of acute serious liver injury or acute liver failure also have been reported.

Children with preexisting liver impairment or viral infection in the liver may be at higher risk of these serious adverse events, and therefore it is recommended that Zolgensma’s risks and benefits be carefully weighed in these patients.

Immune-mediated liver toxicity may require adjustment of the immunosuppressive treatment regimen, including longer duration, higher dose, or extending the dose tapering period. Treatment administered directly into the bloodstream can be considered if oral immunosuppressive therapy is not tolerated.

A pediatric physician specialized in liver or digestive tract organs should be consulted if liver enzyme levels continue to be at least two times higher than the normal upper limit after the 30-day period of immunosuppression.

It also is recommended that Zolgensma treatment not be given to children with clinical signs or symptoms of infection and be postponed until any occurring infection is resolved.

Early this year, thrombotic microangiopathy, a rare condition characterized by blood abnormalities, also was added to the list of safety concerns with Zolgensma use.