Five-Year Data Shows Most Children With Severe SMA on Evrysdi Can Sit, Stand, or Walk

Genentech, part of the Roche Group, has announced new five-year data from the FIREFISH study, showing sustained efficacy and safety of Evrysdi® (risdiplam) for treating children with Type 1 spinal muscular atrophy (SMA). The study's open-label extension reveals that by the end of five years, 91% of children treated with Evrysdi were alive, and 81% were living without permanent ventilation. Importantly, 59% achieved the ability to sit unsupported for at least 30 seconds. Additionally, seven children gained the ability to stand, with three requiring support, four standing unaided, and six capable of walking with assistance. These outcomes are significant given that without intervention, children with Type 1 SMA typically do not survive beyond two years of age and are unlikely to reach such developmental milestones.

Professor Giovanni Baranello from the UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital in London emphasized the study’s importance, noting that Evrysdi-treated children have maintained or improved crucial motor functions over five years, including the ability to sit, stand, and walk. A vast majority also retained their ability to swallow and eat without a feeding tube, which are critical for daily living and development.

Assessments using the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) and Hammersmith Infant Neurological Examination 2 (HINE-2) demonstrated that the motor function abilities of children treated with Evrysdi were either maintained or continued to improve. The FIREFISH study results also indicated that 96% of the evaluated children could swallow and 80% could feed without needing a tube by the end of the fifth year.

Levi Garraway, Genentech’s chief medical officer, highlighted the significance of these findings, stating that the FIREFISH study has provided extensive data confirming Evrysdi as a vital treatment option for enhancing the lives of children with SMA globally. The study's success is attributed to the dedication of the participating children and their families, healthcare professionals, and patient support organizations.

The study reported no treatment-related adverse events leading to discontinuation or withdrawal. The overall adverse event rate reduced by 66% between the first and final year of the study. Common adverse events included upper respiratory tract infections, pyrexia, and pneumonia. Notably, 22% of the children did not require hospitalization at any point during the five-year treatment period.

Evrysdi, an oral, non-invasive small molecule treatment, is unique in its systemic delivery to both the central nervous system and peripheral tissues. Genentech oversees the clinical development of Evrysdi in collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier, indicated for treating SMA caused by mutations on chromosome 5q, leading to SMN protein deficiency. Administered daily in liquid form, either orally or via a feeding tube, Evrysdi increases and sustains SMN protein production in the central nervous system and peripheral tissues. This protein is vital for maintaining motor neuron health and core functions, including swallowing, speaking, and breathing.

Evrysdi has received numerous designations, including PRIME by the European Medicines Agency in 2018 and Orphan Drug by the U.S. FDA in 2017. It has also been recognized with awards such as the British Pharmacological Society’s Drug Discovery of the Year in 2021. Currently, Evrysdi is approved in over 100 countries and is under review in 13 additional countries.

Genentech continues to evaluate Evrysdi in multiple global trials, including FIREFISH and other studies targeting various SMA patient populations and treatment combinations. SMA, a severe and progressive neuromuscular disease, affects approximately 1 in 10,000 babies and is a leading genetic cause of infant mortality. The condition stems from mutations in the SMN1 gene, leading to SMN protein deficiency, which is crucial for the function and survival of motor neurons.