New data show the stark contrast between untreated infants with type 1 spinal muscular atrophy (SMA) and those who received risdiplam.
A new global study of infants with type 1 spinal muscular atrophy (SMA) underscores the devastating natural course of the disease, but also highlights the potential of new disease-modifying therapies.
SMA is a progressive neuromuscular disease caused by a loss of functional survival motor neuron (SMN) protein associated with mutations or deletions of the SMN1 gene. The disease is typically classified based on severity and age of onset. The most common type is type 1 SMA, in which patients experience symptom onset as infants, are never able to sit without assistance, and usually do not live past the first few years of life if the disease goes untreated. Until recently, there were no treatment options available, but 3 drugs have been approved since 2016.
The new data come from the ANCHOVY study, a multicenter chart-review study that was designed to describe type 1 SMA outcomes from a broad geographical area. In a new article in the Orphanet Journal of Rare Diseases, authors from Toulouse University Hospital in France explained the results of the ANCHOVY trial and compared its outcomes with those of the FIREFISH trial of the SMA therapy risdiplam (Evrysdi).
The ANCHOVY trial began in 2008, 8 years before the FDA approved the first treatment for SMA. The study identified 60 patients who met the inclusion criteria of experiencing their first SMA symptoms between 28 days and 3 months of age, received genetic confirmation of SMA, and had 2 copies (or an unknown number of copies) of the SMN2 gene. Those patients spanned 4 continents (Asia, Europe, North America, and South America). The primary end points were death and/or permanent ventilation and the proportion of patients who achieved motor milestones.
The outcomes were stark. The median age for reaching either death or permanent ventilation was 7.3 months, with an IQR of 5.9 to 10.5 months. The median age for permanent ventilation was 12.7 months, and the median age at death was 41.2 months.
None of the patients were ever able to sit without support, and none reached the milestones of crawling, standing, or walking.
The authors noted that those outcomes align with previous literature from the pretherapy era.
Conversely, the FIREFISH study showed that 12 of 41 infants treated with risdiplam were able to sit without support after 12 months of treatment, and 85% of the infants were alive without the need for permanent ventilation.
“While demographic and baseline disease characteristics were comparable between the ANCHOVY and FIREFISH Part 2 studies, the marked difference in event-free survival, achievement of motor milestones and initiation of feeding support for FIREFISH Part 2 participants compared with ANCHOVY patients further supports the benefit of risdiplam in patients with Type 1 SMA,” the authors concluded.
In addition to providing evidence of the benefits of therapy, the investigators said the ANCHOVY data were also useful because they spanned a greater geographic area than did previous research and therefore confirmed that data were similar across the world, even outside of the United States and Europe, which have been the settings for most of the existing literature.
Cances C, Vlodavets D, Comi GP, et al. Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study. Orphanet J Rare Dis. 2022;17(1):300. doi:10.1186/s13023-022-02455-x