Onasemnogene abeparvovec commonly linked to hepatotoxicity

Hepatotoxicity is common after treatment with onasemnogene abeparvovec (OA) for spinal muscular atrophy (SMA), a recent study has found. Clinicians should anticipate and be ready to manage such adverse events, and be aware of any potential underlying conditions that could aggravate them.

The study included a total of 325 SMA patients who had been treated with OA through 31 December 2019. Outcomes included liver-related adverse events and laboratory data. Participants were enrolled from five clinical trials, a long-term registry, a managed access programme, and post-marketing monitoring.

Clinical studies contributed data from 100 patients (mean age, 2.9 months, 59 percent girls). All patients had received OA intravenously, and 99 experienced at least one adverse event after administration. Fifty-seven of these events were deemed related to the drug. Forty-eight patients experienced adverse events, of which 11 were judged to be related to OA.

Moreover, 34 percent of patients from clinical study developed adverse events that could be defined as hepatotoxicity.

In terms of laboratory data, 90 percent had at least some degree of elevation in alanine (ALT) or aspartate (AST) aminotransferases during therapy. Most elevations were slight, though 5 percent were categorized as severe, reaching ≥20 times the upper level of normal.

Data of 43 patients were included from open-access sources, such as registries and access programmes. These confirmed the principal findings from clinical studies: 65.1 percent experienced adverse events and 30.2 percent had serious episodes of such events. Liver function tests and levels of AST and ALT were also commonly increased after OA.

Post-marketing data were not collected systematically and therefore had inconsistencies. Pooling reports, however, showed that common side-effects included pyrexia, vomiting, and increases in hepatic enzymes, ALT, and AST.

“Hepatotoxicity is a known risk associated with OA use. Practitioners should identify contributing factors and mitigate risk through appropriate monitoring and intervention,” the researchers said.