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

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.