Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study

Abstract

Abstract Background ANCHOVY was a global, multicenter, chart-review study that aimed to describe the natural history of Type 1 spinal muscular atrophy (SMA) from a broad geographical area and provide further contextualization of results from the FIREFISH (NCT02913482) interventional study of risdiplam treatment in Type 1 SMA. Methods Data were extracted from medical records of patients with first symptoms attributable to Type 1 SMA between 28 days and 3 months of age, genetic confirmation of SMA, and confirmed survival of motor neuron 2 copy number of two or unknown. The study period started on 1 January 2008 for all sites; study end dates were site-specific due to local treatment availabilities. Primary endpoints were time to death and/or permanent ventilation and proportion of patients achieving motor milestones. Secondary endpoints included time to initiation of respiratory and feeding support. Results Data for 60 patients from nine countries across Asia, Europe and North and South America were analyzed. The median age (interquartile range [IQR]) for reaching death or permanent ventilation was ~ 7.3 (5.9–10.5) months. The median age (IQR) at permanent ventilation was ~ 12.7 (6.9–16.4) months and at death was ~ 41.2 (7.3–not applicable) months. No patients were able to sit without support or achieved any level of crawling, standing or walking. Interpretation Findings from ANCHOVY were consistent with published natural history data on Type 1 SMA demonstrating the disease’s devastating course, which markedly differed from risdiplam-treated infants (FIREFISH Part 2). The results provide meaningful additions to the literature, including a broader geographical representation.

Keywords

• ANCHOVY
• FIREFISH
• SMA natural history
• Type 1 SMA
• Spinal muscular atrophy