Vg/kg = vector genomes/kilogram

SMA = Spinal Muscular Atrophy

AAV9 = Adeno-associated virus serotype 9

CHOP-INTEND: Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, a motor assessment tool devised for infants with SMA. This has 16 items graded on a scale of 0 to 4, with 0 being no response and 4 being complete response.

Spinal muscular atrophy (SMA) is a severe neurodegenerative condition resulting from recessive mutations in the SMN1 gene and insufficient survival motor neuron (SMN) protein production.1 Lack of SMN protein causes irreversible degeneration of lower motor neurons and consequential muscle atrophy and weakness. Onasemnogene abeparvovec, marketed under the name Zolgensma, directly replaces the SMN1 gene using a non-replicating, non-pathogenic modified adeno-associated virus serotype-9 (AAV9). In this article, we outline the patient selection process for treatment with onasemnogene abeparvovec, with some illustrative clinical examples.

In the USA, onasemnogene abeparvovec has been approved for the treatment of children with SMA, (including SMA type 2) up to the age of 2 years; in Europe including the UK, it has been approved for treatment of patients with 5q SMA with a biallelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1, or patients with 5q SMA with a biallelic mutation in the SMN1 gene and up to three copies of the SMN2 gene and presymptomatic infants with up to three SMN2 copies. In Australia, the drug is indicated for the treatment of children less than 9 months of age with symptomatic or presymptomatic SMA with biallelic mutations in the SMN1 gene and one to three copies of the SMN2 gene. In Japan, this is approved for the treatment of SMA in patients under the age of 2 years, including those who are presymptomatic at diagnosis.

Onasemnogene abeparvovec is infused intravenously over 1 hour. The dose …