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Results of an observational study of efficacy and safety data for Zolgensma in young under-studied patient populations, including children older than 24 months at treatment and those who have previously received nusinersen, were recently published in the October 2021 Lancet medical journal.

The study was conducted in neuromuscular centres across Germany and Austria between September 2019 and April 2021, and involved 76 children with SMA Types 1 and 2; 58 children had previously received treatment with nusinersen and 18 had not (“nusinersen naïve”). The motor function of each child was assessed as a baseline at the time of treatment with Zolgensma and then again 6 months later, using both the CHOP-INTEND and HFMSE functional scales. The mean age at which the children were treated was 16.8 months (ranging from 0.8 to 59.0 months), and their mean weight was 9.1 kg (ranging from 4.0 to 15.0 kg). Zolgensma was delivered intravenously.

Results from all children

At the time of publication (October 2021), data were generated from 60 children. Following treatment with Zolgensma, at the 6 months assessment, 49 children showed an improvement of more than or equal to 4 points on the CHOP-INTEND scale or 3 or more points on the HFMSE scale. Ten children showed no change, whereas one displayed a reduction in score (although this was thought to be linked to a case of pneumonia).

The mean CHOP-INTEND score after 6 months increased in children who received Zolgensma treatment at 8 months or younger (average improvement of 13.8 points). Motor function also improved in children treated between 8 and 24 months of age (average improvement of 7.7 points). However, children receiving Zolgensma at 24 months or older did not show a consistent improvement.

Results for children pre-treated with nusinersen

In children pre-treated with nusinersen, there was an average increase of 8.8 points in the CHOP-INTEND score 6 months after treatment with Zolgensma. The pre-treatment of children with nusinersen had occurred for on average 12.4 months.

Results for nusinersen naïve children

An average increase of 9.4 points was reported in the nusinersen naïve children, although this cohort was much younger.

Thus strong conclusive comparisons about the two cohorts cannot be made.

Adverse Effects

For all groups, no immediate complications occurred during the Zolgensma treatment process; however, treatment-related side-effects were reported within the first 7 days after treatment in 74% of children, including serious adverse events in eight children (11%). The reported adverse events include acute liver dysfunction (8%, “severe”), fever (62%), vomiting or loss of appetite (54%), and fatigue (12%). Furthermore, two children displayed heart-related abnormalities.

It is unclear from the study whether adverse events were more common in children pre-treated with nusinersen compared with nusinersen naïve children. However, elevation of liver enzymes was higher in children pre-treated with nusinersen.


Overall, the study shows that Zolgensma treatment provides a considerable boost to the muscle function of SMA children within the age and weight range of the children in the study, including those who have previously received treatment with nusinersen. The improvements were best when Zolgensma was given before 2 years of age, after which the positive impact was limited. The study also supports that Zolgensma is generally well tolerated, but that patients must be monitored closely for several days after treatment for adverse events, which are common and can sometimes be severe, though manageable via intervention.

Original publication (paywall) >