Long-term treatment with Fabrazyme (agalsidase beta), an enzyme replacement therapy for people with Fabry disease, slows the progression of kidney disease and significantly delays arriving at outcomes that include heart or kidney failure, results from clinical and real-world studies show.
Findings from this work — a Phase 4 clinical trial that followed patients for up to nearly three years, and a real-world, observational study that ran for up to five years — are now included in the therapy’s U.S. label.
“These findings are a remarkable contribution to the on-going understanding of this rare disease and the long-term impact of Fabry on renal function and clinically significant events,” Robert J. Desnick, MD, PhD, the trial’s lead investigator and dean for Genetics and Genomic Medicine at the Icahn School of Medicine at Mount Sinai, said in a press release.
Administered as an infusion into the bloodstream every two weeks, the therapy works by replenishing the levels of alpha-galactosidase A — the enzyme responsible for breaking down a fatty molecule called globotriaosylceramide (Gb3) and missing in Fabry patients.
Fabrazyme has been approved since 2003 based on data from multiple clinical trials, but its long-term benefits have not been well described.
To address that, researchers conducted a Phase 4 trial (NCT00074984) of Fabrazyme’s use in Fabry patients who had not received prior ERT. Essentially, Phase 4 trials are conducted after a drug has been approved to determine its long-term safety and efficacy in real-life scenarios.
This trial, called Study 2 and underway from 2001 to 2004 at 26 sites in North America and Europe, enrolled 82 adults (median age of 45, range 20 to 72) who were randomly assigned to Fabrazyme or placebo for up to 35 months.
Its main goal was the number of patients who experienced a clinically significant event — including events like kidney dialysis or transplant, heart attack or failure, stroke, and death.
After a median of 18.5 months, 14 out of 51 Fabrazyme-treated patients (28%) had at least one such event, compared with 13 of the 31 patients (42%) assigned to placebo. This represented a 33% reduction in the risk of such events.
Patients on Fabrazyme also showed a drop in their blood Gb3 levels, from 9 micrograms/mL (mcg/mL) before treatment to 4.8 mcg/mL after one and two years of its use. These levels remained close to 9 mcg/mL at all timepoints in placebo-treated patients.
In the observational study, researchers investigated the rate of decline in kidney function among 122 patients, ages 16 and older, treated with Fabrazyme and compared these rates to a group of 122 historical controls — those with untreated disease and matched to patients in terms of age, sex, disease subtype (classic or non-classic), and initial kidney function.
Patients in this study, dubbed Study 5, were followed for a median of 4.5 years, while untreated controls had a median follow-up of three years. The maximum a patient was followed in any group was five years.
Real-world data here showed that kidney function — measured with the estimated glomerular filtration rate (eGFR) — was better preserved in patients using Fabrazyme over time than was evident in the historical group.
Patients on Fabrazyme experienced a decline in their eGFR scores of 1.5 mL per minute per 1.73 m2 each year, while the annual decline for controls was 3.2 mL per minute per 1.73 m2 each year — a difference of 1.7 points.
“We express our deepest gratitude to the thousands of patients, physicians and researchers who have contributed to the understanding of Fabry disease over the past two decades,” said Alaa Hamed, MD, global head of rare disease medical affairs at Sanofi. “We believe this evidence builds on the overall understanding of the efficacy and safety profile of Fabrazyme.”
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