Clinical observation of patients with Fabry disease after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal)

Abstract

Purpose:Fabry disease is a rare, X-linked, inherited lysosomal storage disorder that can be treated with the enzymes agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). Currently, there is a global shortage of agalsidase beta, and this has increased global demand for agalsidase alfa. We assess the feasibility of switching patients on agalsidase beta treatment to agalsidase alfa instead.Methods:This analysis is part of an ongoing observational study involving 11 patients with Fabry disease in whom the treatment was switched from agalsidase beta (1 mg/kg every other week) to agalsidase alfa (0.2 mg/kg every other week). Data were collected for a minimum of 36 months: 24 months before and 12 months after the switch. Serial data were evaluated with respect to renal function, cardiac mass, pain, quality of life, and tolerability/safety.Results:Indexes of renal function (estimated glomerular filtration rate) and cardiac mass (left-ventricular mass index), pain (Brief Pain Inventory), and quality of life (EuroQoL-Dimensions) clearly showed that, in patients switched to agalsidase alfa, Fabry disease stabilized during the 12 months of follow-up.Conclusion:Despite the limitations of this preliminary observational study, it was found that all the patients maintained disease stability when treated with agalsidase alfa, as evidenced by estimated glomerular filtration rate, left-ventricular mass index, pain scores, and quality-of-life indexes, throughout 12 months of follow-up.

Effects of Switching from Agalsidase Beta to Agalsidase Alfa in 10 Patients with Anderson-Fabry Disease

“…The switch in treatment was generally well tolerated. These results largely confirm those reported by Tsuboi et al in a similarly designed study in 11 Japanese patients with Anderson-Fabry disease (Tsuboi and Yamamoto 2012). In their study, eGFR also remained stable when patients switched to agalsidase alfa.…”

“…In their study, eGFR also remained stable when patients switched to agalsidase alfa. Unlike the current study, their echocardiographic findings suggested improvements in LV mass index and wall thickness after 12 months agalsidase alfa treatment compared with agalsidase beta treatment (Tsuboi and Yamamoto 2012). They reported a similar lack of increase in pain symptoms or deterioration in quality of life with the switch in treatment to the current study.…”

“…The current study did not measure plasma or myocardial Gb3 levels; thus, whether myocardial Gb3 deposits were reduced after sustained ERT for 48 months with agalsidase beta and then 20 months with agalsidase alfa in this study is not known. The Tsuboi et al switch study did not measure myocardial Gb3 levels either, but their patients experienced an increase in plasma Gb3 levels after the switch from agalsidase beta to alfa treatment (Tsuboi and Yamamoto 2012). Nevertheless, patients still experienced reductions in LV mass after the switch.…”

“…An expert consensus guidelines published in 2011 recommended a similar approach (Linthorst et al 2011). Data on the effect of switching between the two therapies are limited to one observational study in 11 Japanese patients (Tsuboi and Yamamoto 2012) and a subgroup of 20 patients in a retrospective cohort Dutch study (Smid et al 2011). Both reported clinical outcomes, including effects on cardiac abnormalities, but neither assessed cardiac effects via cardiac magnetic resonance imaging (cMRI).…”

Successful Management of Enzyme Replacement Therapy in Related Fabry Disease Patients with Severe Adverse Events by Switching from Agalsidase Beta (Fabrazyme®) to Agalsidase Alfa (Replagal®)

“…Recently, an observational study involving 11 patients with Fabry disease who were switched from agalsidase beta to agalsidase alfa showed that indices of renal function, cardiac mass, pain and quality of life were maintained after switching (Tsuboi and Yamamoto 2012). Another study found that a reduced dose of agalsidase beta was not associated with an increase in the incidence of clinical events compared with the full dose, and neither was a switch to agalsidase alfa (Smid et al 2011).…”