On March 27, European Medicines Agency (EMA) recommended granting a conditional marketing authorisation in the European Union for the gene therapy Zolgensma (onasemnogene abeparvovec) to treat babies and young children with spinal muscular atrophy (SMA). This was based on the assessment and positive opinion of the Committee for Advanced Therapies (CAT), EMA’s expert committee for cell- and gene-based medicines, and EMA’s Committee for human medicines (CHMP).
This therapy was approved in the USA about one year ago and recently in Japan. Zolgensma is an adeno-associated virus (AAV) 9 based gene therapy designed to deliver a fully functioning copy of the human SMN1 gene enabling the body to produce enough SMN protein.
The treatment is indicated for children with 5q SMA with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1; or patients with 5q SMA with a bi-allelic mutation in SMN1 and up to three copies of the SMN2 gene.
Zolgensma should be administered in a single intravenous (IV) infusion.
EMA’s recommendation for conditional marketing authorisation is based on the preliminary results of one completed clinical trial and three supporting studies in patients with SMA with different stages of disease severity. These included genetically diagnosed and pre-symptomatic patients.
The clinical trial was conducted in 22 patients who were < 6 months of age at the time of the gene replacement therapy with Zolgensma. The trial assessed the percentage of patients who had improvement in their survival (i.e. without the need to be permanently on a ventilator) and motor milestones, such as head control, crawling, sitting, standing and walking (with or without assistance). Out of 22 patients enrolled in the trial, 20 patients (91%) were alive and did not need permanent ventilatory support at 14 months of age, in contrast to the natural history of the disease showing that at 14 months of age only 25% of patients are still alive. The treated patients also achieved motor milestones, which are usually not achieved in untreated patients: 14 patients (64%) reached the milestone of independent sitting < 18 months of age. Less affected patients appeared to benefit the most from the treatment with Zolgensma.
This conditional approval could lead to full EMA approval within the next couple of months. It is a major step towards offering a new treatment option in Europe for babies and young children with SMA.
Dr Anna Ardissone, Milan, Italy and Prof. Svetlana Hadjiu, Chisinau, Republic of Moldova, are both members of the EAN Scientific Panel on Rare neurological Diseases.