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

## TL;DR

A 20-year study shows agalsidase alfa treatment for Fabry disease is effective and safe, with benefits on kidney and heart health in adults.

## Contribution

The study provides long-term evidence of agalsidase alfa's effectiveness and safety in Fabry disease patients over 20 years.

## Key findings

- Annualized changes in eGFR remained stable in females and slightly declined in males.
- LVMI remained stable in both genders during treatment.
- Treatment improved morbidity and mortality outcomes compared to natural disease progression.

## Abstract

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).

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.

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 m2 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 m2). At baseline, mean (SD) LVMI was 58.25 (25.01) g/m2.7 and LVMI (slope [SE]) remained stable (.34 [.16] vs. .38 [.15] g/m2.7/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.

This report further supports the long‐term effectiveness and safety of agalsidase alfa in adults with Fabry disease.

Long‐term treatment with agalsidase alfa in 1864 adults with Fabry disease in the Fabry Outcome Survey confirmed previously reported beneficial effects on renal function and cardiomyopathy. Over a median (min, max) of 6.0 (0, 21.6) years of treatment, annualized changes in eGFR remained relatively stable in females and declined slightly in males. LVMI remained stable in females and males. Beneficial effects were also seen on morbidity and mortality versus Fabry disease natural history data. Agalsidase alfa was generally well tolerated.