Symptomatic Type 1 spinal muscular atrophy (SMA) infants treated with Evrysdi (risdiplam) showed significant improvements in survival, motor milestones, and motor function compared to historical controls, according to findings from the FIREFISH Part 2 study, which have been published in the New England Journal of Medicine (NEJM).
This pivotal global study sought to evaluate the efficacy and safety of Evrysdi (risdiplam) in babies aged between one and seven months old with symptomatic Type 1 SMA.
The study met its primary endpoint with 29% of infants (12/41) sitting without support for at least five seconds by month 12, a milestone not seen in the natural course of the disease.
Additionally, at month 12, 93% (38/41) of infants were alive and 85% (35/41) were free from permanent ventilation. Without treatment, the median age of death or permanent ventilation was 13.5 months in a natural history cohort. A total of 90% (37/41) had a CHOP-INTEND (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders) score increase of at least four points, with 56% (23/41) achieving a score above 40; the median increase was 20 points.
Laurent Servais, FIREFISH investigator and professor of paediatric neuromuscular diseases at the MDUK Oxford Neuromuscular Centre (Oxford, UK), said: “Without treatment, babies with Type 1 SMA are unlikely to survive beyond two years of age.
“Important motor milestones, such as sitting, rolling over and swallowing, are the fundamental building blocks that can help these babies achieve optimal outcomes with Evrysdi, potentially reducing the need for ventilation and increasing the rate of survival.”
At the time of the data analysis, the median duration of treatment with Evrysdi was 15.2 months and the median age was 20.7 months.
The study also met one of its secondary endpoints with 78% (32/41) of infants classified as HINE-2 (Hammersmith Infant Neurological Examination 2) responders, which evaluated motor function through head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing and walking. Infants were classified as HINE-2 responders if more motor milestones showed improvement than worsened.
Safety for Evrysdi in the FIREFISH Part 2 study was consistent with its known safety profile. The most common adverse events were upper respiratory tract infection (68%), pneumonia (39%), pyrexia (39%), constipation (20%), diarrhoea (10%) and maculopapular rash (10%).
The most common serious adverse events were pneumonia (32%), bronchiolitis (5%), hypotonia (5%) and respiratory failure (5%). Three infants experienced fatal complications of their disease within the first three months of treatment. None of these were attributed by the investigator as related to Evrysdi.
Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.
Evrysdi is designed to treat SMA by increasing and sustaining the production of the SMN protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.
Evrysdi was granted orphan designation by the European Medicines Agency (EMA) in 2019, PRIME designation by the EMA in 2018 and Orphan Drug Designation by the US Food and Drug Administration in 2017. Evrysdi has been approved in 54 countries and submitted in a further 33 countries.