Long-term agalsidase alfa shows benefits as Fabry disease treatment
Use over 20 years extends survival, aids kidney, heart function: Study
Up to 20 years of treatment with agalsidase alfa slowed declines in kidney and heart function, and extended survival, among people with Fabry disease, according to the findings of a global real-world study.
The therapy’s long-term use was found to delay mortality in these patients relative to untreated people with Fabry disease.
The researchers also noted that kidney outcomes improved and heart muscle disease stabilized “regardless of sex or [a patient’s] baseline” status — a participant’s functional levels or condition at the study’s start.
Still, among male Fabry patients, kidney function declined faster, and the probability of survival over time was lower, compared with female patients, the data showed.
Overall, however, the researchers concluded that “long-term treatment with agalsidase alfa may provide renal [kidney], cardiac, and overall survival protection in [Fabry disease].”
The study, “Two decades of experience of the Fabry Outcome Survey provides further confirmation of the long-term effectiveness of agalsidase alfa enzyme replacement therapy,” was published in the journal Molecular Genetics and Metabolism Reports.
Investigating the long-term use of agalsidase alfa in Fabry
Agalsidase alfa is an enzyme replacement therapy (ERT) that provides a functional version of alpha-galactosidase A, the enzyme that’s missing in people with Fabry. Sold under the brand name Replagal, it’s been approved in the European Union since 2001 and is authorized in many other countries worldwide; however, it is not cleared for use in the U.S.
In this study, sponsored by Takeda Pharmaceuticals, which markets agalsidase alfa, a global team of researchers examined the long-term effectiveness of the ERT.
The team used data spanning as long as 20 years from the Fabry Outcome Survey (NCT03289065). This international, observational study intends to provide long-term data on the effectiveness and safety of approved treatments for Fabry — and seeks to better understand the disease and improve how it is treated.
Treatment outcomes were compared with those of untreated patients from previously published studies.
A total of 2,171 people — 1,014 men, 919 women, 163 boys, and 75 girls — received agalsidase alfa for a median duration of 5.38 years, with a range of up to nearly 21 years. Most patients (about 80%) had classic Fabry, while the remaining individuals (about 20%) had late-onset, or non-classic, disease.
The annual rate of kidney function decline in treated patients was numerically lower than that of untreated individuals, regardless of sex, as assessed by the estimated glomerular filtration rate (eGFR). Still, kidney function declined significantly faster in treated male patients than in female patients.
Male patients lost kidney function faster each year than female patients, independently of how long they had been treated. When looking at treatment length, women who had been treated for less than 10 years had a faster decline in kidney function compared with those treated for 10 years or more, the data showed.
Cardiomyopathy, a disease of the heart muscle, worsened more slowly in treated versus untreated patients, regardless of sex or treatment duration, as indicated by the annual left ventricular mass index (LVMI). Even so, the annualized LVMI changes of treated patients with or without left ventricular hypertrophy, or the enlargement of the heart’s left lower chamber, were similar, regardless of sex.
Fabry disease treatment seen to extend patient survival
The team then analyzed morbidity, or the general state of illness, by assessing the occurrence of a composite event, which included adverse heart events/procedures, kidney events, stroke, or death.
In treated patients, men were generally younger than women at their first composite event (mean 40.23 vs. 49.14), but the time to an event from the start of treatment was similar between the two sexes.
Overall, treated patients were older than untreated patients at the time of their first composite event. After two years of treatment, the likelihood of a composite morbidity event was lower in treated than untreated patients (34% vs. 45%), particularly among boys/men (46.6% vs. 87%).
In a survival analysis, patients who were treated lived longer than those who were untreated, by an average (mean 61.7 vs. 50.3 years). Although the age at which half of the treated male patients were still alive was older than that of untreated patients (75.5 vs. 60 years), treated boys/men had a lower probability of survival over time than treated girls/women.
Overall, these findings indicate a positive impact of agalsidase alfa treatment on renal [kidney] outcomes, as well as a stabilization or slowing of [heart disease] progression and delayed … mortality in treated patients.
When researchers compared the two types of Fabry, kidney function declined faster in treated male patients with classic Fabry than in those with late-onset disease, but not in female patients. Alterations in the annual LVMI rates of change were similar in male and female patients, regardless of Fabry type.
Lastly, treated patients with classic Fabry had a longer time from the beginning of treatment to the first composite event, regardless of sex, but died at a younger age than those with late-onset Fabry (mean 47.36 vs. 59.51 years).
“Overall, these findings indicate a positive impact of agalsidase alfa treatment on renal outcomes, as well as a stabilization or slowing of cardiomyopathy progression and delayed morbidity and mortality in treated patients when compared with untreated comparator cohorts,” the researchers wrote.
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