Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study

Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma®) for the SMA Rare Disease: A Pharmacovigilance Study Based on the EMA Adverse Event Reporting System

“…As regards the types of adverse events, our results were in line with the recently published Zhuang et al study [ 33 ]. Both pharmacovigilance studies highlighted a higher reporting of pyrexia, vomiting, increased aspartate aminotransferase, increased alanine aminotransferase, thrombocytopenia, increased transaminases, and increased liver enzymes, as ADRs related to the SMA gene therapy.…”

“…Regarding the sex distribution, although some evidence suggests that males may be more vulnerable to SMA than females [ 34 , 35 ], our analysis revealed a greater reporting of ADRs in female patients. This result, as well as the major distribution in terms of the reporter type in favor of HPs, is in line with the analysis conducted by Zhuang et al on the US database [ 33 ]. As described in other studies, HPs represent the major reporting source, even if, to date, citizens can also send safety reports to regulatory authorities [ 36 , 37 ].…”

“…Our reporting trend differed compared with the trend that emerged from a recent study conducted on the US pharmacovigilance database [33]. Following the surge in the Zolgensma ® -related ADR reporting in 2020 compared with 2019, the authors found a decreasing trend in the number of reports collected until 2022 in the US database, the Food and Drug Administration Adverse Event Reporting System (FAERS) [33]. Regarding the sex distribution, although some evidence suggests that males may be more vulnerable to SMA than females [34,35], our analysis revealed a greater reporting of ADRs in female patients.…”

“…Excluding the partial data referred to 2023, the annual reporting trend was growing up to 2022. Our reporting trend differed compared with the trend that emerged from a recent study conducted on the US pharmacovigilance database [ 33 ]. Following the surge in the Zolgensma ® -related ADR reporting in 2020 compared with 2019, the authors found a decreasing trend in the number of reports collected until 2022 in the US database, the Food and Drug Administration Adverse Event Reporting System (FAERS) [ 33 ].…”

“…Furthermore, it is important to note that, in both studies, a risk of damage to the heart was highlighted, evidenced by an increase in troponin blood concentrations. According to Zhuang et al, such increased levels of troponin I and T have been identified as idiosyncratic adverse reactions to onasemnogene abeparvovec [ 33 ]. However, the possible causal relationship and the biological plausibility between onasemnogene abeparvovec treatment and cardiotoxicity is still unclear.…”