Novartis has reported two patient fatalities as a result of acute liver failure following treatment with the company’s spinal muscular atrophy (SMA) treatment Zolgensma (onasemnogene abeparvovec).
The company has notified health authorities, including the US Food and Drug Administration (FDA), in markets where the drug is sold and has informed relevant healthcare professionals as an additional step.
The two fatal cases of acute liver failure – which were seen in children – took place in Russia and Kazakhstan after five to six weeks after administration of Zolgensma. Both children died after corticosteroid medicines – which were used to reduce the risk of side effects after treatment – began to be tapered off.
The company said it will update Zolgensma’s label to specify that fatal acute liver failure has been reported, however it stated that it is ‘not a new safety signal’.
SMA is a disease affecting an estimated one in 10,000 infants globally. If the condition is left untreated, patients with two copies of the survival motor neuron (SMN)2 gene will typically go on to develop SMA type 1, leading to a progressive and irreversible loss of motor function and, in the majority of cases, death or permanent ventilation by the age of two.
The deaths are the first fatal cases of acute liver failure that have been linked to Zolgensma, a gene therapy developed by AveXis – which Novartis acquired in a $8.7bn deal in 2018.
In May 2019, Zolgensma was approved by the FDA for the treatment of SMA in paediatric patients less than two years of age with SMA with bi-allelic mutations in the survival motor neuron 1 gene, making it the second gene therapy authorised by the FDA for an inherited disease.
To date, more than 2,300 patients have been treated with Zolgensma worldwide. In June, Novartis published final results from a phase 3 trial assessing Zolgensma, which showed that almost all children with two or three copies of the SMN2 gene treated pre-symptomatically had met key milestones including sitting, walking and standing.
Zolgensma is currently administered intravenously, meaning treatment is limited to younger children under a certain weight. However, the company is exploring intrathecal dosing of the gene therapy, whereby an injection is given directly into the cerebrospinal fluid through the lower back.
The new method is being studied in a phase 3 trial in patients aged two to 18-years-old who have SMA type 2, who have never walked and who have never received a prior treatment for SMA.