Long‐term effectiveness and safety outcomes in adults with Fabry disease treated with agalsidase alfa: 20 years of data from the Fabry Outcome Survey

Background We present the final report from the Fabry Outcome Survey (FOS) on long‐term effectiveness and safety of agalsidase alfa in adults (≥18 years old). Methods FOS was an international, multicentre, observational registry (NCT03289065), designed to enhance the understanding of Fabry disease and improve clinical management. Primary effectiveness endpoints were annualized change in estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI), and time to and age at composite morbidity event (comprising renal, cardiac or stroke events) and death. Safety outcomes were also assessed. Results FOS included data for 1864 adults (female/male, n = 907/957) who received agalsidase alfa only for a median (minimum, maximum) of 6.0 (0, 21.6) years, and 1613 untreated adults (female/male, n = 1235/378). At baseline, mean (standard deviation [SD]) eGFR was 94.01 (27.60) mL/min/1.73 m 2 in treated adults; annualized changes in eGFR (slope [standard error; SE]) remained relatively stable in females and declined slightly in males (−1.07 [.12] vs. −2.17 [.12] mL/min/1.73 m 2 ). At baseline, mean (SD) LVMI was 58.25 (25.01) g/m 2.7 and LVMI (slope [SE]) remained stable (.34 [.16] vs. .38 [.15] g/m 2.7 /year in females and males, respectively). Time (median [95% confidence interval]) from treatment initiation to first composite event was longer for females than males (83.4 [65.7–98.0] vs. 56.3 [45.6–66.7] months); age (median [minimum, maximum]) at death was also higher for treated females than males (69.9 [32.5, 87.7] vs. 59.1 [26.2, 79.6] years). Agalsidase alfa was generally well tolerated. Conclusions This report further supports the long‐term effectiveness and safety of agalsidase alfa in adults with Fabry disease.