Onasemnogene Abeparvovec Effective in Treatment of Older, Heavier Children with SMA

No serious long-term safety issues were recorded with the use of the gene therapy onasemnogene abeparvovec (OA; Zolgensma) in the treatment of children with spinal muscular atrophy (SMA) type 1, according to a study published in The Lancet Regional Health – Europe.

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OA is 1 of 3 approved therapies in the treatment of SMA and utilizes a vector of a genetically modified adeno-associated virus type 9 (AAV9) in its stimulation of functional SMN protein production. As authors of the present study note, multiple previous studies have demonstrated that OA can provide benefits to the survival and motor function of children under 2 years of age with SMA types 1 and 2; however, data on the efficacy and safety of OA in children beyond 2 years, as well as those weighing more than 13.5 kg, is lacking.

To address this gap in knowledge, researchers conducted a multi-center analysis in the UK to gather real-world data on the use of OA in patients with SMA type 1, which included those 2 years of age or older and weighing at least 13.5 kg.

Data were gathered on pediatric patients with SMA type 1 administered OA from May 2021 to January 2023. Researchers analyzed patients in conjunction with the SMAREACH registry throughout 6 UK infusion centers. Individuals’ platelet counts, liver function, need for steroids, and cardiac assessments were evaluated in the safety analysis of OA. Additional scales such as the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Infant Neurological Examination (HINE), and Revised Hammersmith Scale (RHS) were used in patient assessments. Investigators reviewed the highest individual score achieved during follow-ups as well as scores 2 weeks prior. Furthermore, patients were categorized according to their age and weight at the time of infusion: younger than 6 months, 6 to 12 months, 1 to 2 years, older than 2 years; and less than 8.5 kg, 8.5 to 13.5 kg, and at least 13.5 kg.

A total of 99 patients with SMA treated with OA were included, 45 of whom were treatment naïve. The other 54 patients were referred to as the pre-treatment cohort. Twenty-one patients were at least 2 years old and 7 were at least 13.5 kg. Follow-ups ranged between 3 and 22 months.

CHOP-INTEND scores were available before and after OA initiation for 78 patients. Overall, 84.6% (66) of patients registered increases in their scores, with a mean change of 11 points across the cohort. Notably, patients younger than 6 months had statistically significant increases in CHOP-INTEND over patients aged 2 years or older (13.9-point gains; 95% CI, 6.8-21.0; P < .001). Each age group trended positively in this regard; however, patients aged younger than 6 months experienced significantly higher estimated increases than both patients aged 6 to 12 months (P = .03) and those 12 to 24 months of age (P < .001).

Those who completed RHS and HINE assessments also demonstrated functional scoring increases, but these examinations were not done across the majority of the cohort.

Investigators witness that a patient’s weight at infusion was positively correlated with steroid administration (P < .001). For each increase of 5 kg of weight, individuals were linked to 46% longer durations of steroid use (95% CI, 24.1%-71.7%). Furthermore, the multivariable analysis revealed that there was also an association between age of infusion with OA and steroid duration (P < .001), with each 1-year age increase associating with a 13.8% extended period of steroid therapy (95% CI, 7.2%-20.7%).

The authors note that hepatoxicity was also more associated with increased weights in these patients, and that a few endured worsening transaminitis; however, any clinical issues were nonpersistent in older and heavier patients. As OA treatment was well-tolerated and contributed to functional betterment, these findings demonstrate the safety and efficacy of OA in this population.

Reference

Gowda V, Atherton M, Murugan A, et al. Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom. Lancet Reg Health Eur. Published online December 11, 2023. doi:10. 1016/j.lanepe.2023.100817