New Studies Affirm Safety Profile, Efficacy of Agalsidase Beta in Fabry Disease

About 1 in 3 patients experienced adverse drug reactions in the 2 new safety studies, aligning with earlier reports.

Agalsidase beta is effective over the long term and has an acceptable safety profile in patients with Fabry disease (FD), according to a pair of new postauthorization safety studies.

The studies, which were undertaken in Japan and published in the journal Expert Opinion on Drug Safety, add extensive detail to the available data regarding the safety of the enzyme replacement therapy (ERT).

Since its inception nearly 2 decades ago, ERT has become a “mainstay” of treatment for FD, according to corresponding author Mina Tsurumi, of Sanofi Genzyme Medical, and colleagues. Agalsidase beta, sold under the brand name Fabrazyme, is a recombinant form of human α-galactosidase A, the lysosomal enzyme deficient or missing in patients with FD. It has been approved in the United States and European Union since the early 2000s, and was approved in Japan in 2004.

The therapy has been linked with increased enzymatic activity in human Fabry cells and mouse cells, and has been shown to generate higher levels of activity in cultured fibroblasts, kidneys, heart, and spleen samples, compared to the other available ERT, agalsidase alfa.

Yet, the investigators noted that only 13 patients with Fabry disease were enrolled in the registration clinical trials in Japan. Tsumuri and colleagues sought to provide more robust safety and efficacy data by undertaking 2 postauthorization safety studies. The new studies include a Special Drug Use Investigation monitoring the long-term safety and efficacy of the therapy, and a Drug Use Investigation that looked at the same factors in patients not participating in the former study.

Altogether, 396 patients were studied, including 332 in the Special Drug Use Investigation and 64 patients in the Drug Use Investigation. Of those, 307 patients gave permission and had sufficient data to participate in the safety analysis, and 196 patients were included in the efficacy analysis.

Adverse drug reactions (ADR) occurred in roughly 1 in 3 patients (30.3%). However, only 8.1% of patients experienced a serious ADR. Of those, general disorders and administration site conditions occurred in 55 patients (17.9%), 30 patients experienced nervous system disorders (9.8%), and 23 patients experienced skin and subcutaneous tissue disorders (7.5%). In 8 cases, patients died during the study and ERT or agalsidase beta could not be ruled out as a cause. Those deaths included single patients who died of suicide, cachexia, pulmonary edema, disseminated intravascular coagulation with pneumonia, cardio-respiratory arrest, and sudden death. Two patients’ deaths were listed as “unexplained.” Twenty-seven patients discontinued treatment due to ADRs.

Still, the safety profile in the new reports is consistent with those of earlier studies, Tsumuri and colleagues wrote, adding that most of those ADRs appeared in the first year after ERT initiation.

In terms of efficacy, the drug reduced blood globotriaosylceramide (GL-3) levels in patients across the study, regardless of age or disease phenotype. The investigators recommended routine antibody testing in patients undergoing ERT, noting that anti-agalsidase beta antibodies developed in 50.5% of patients overall in the studies, a figure lower than the rates reported in earlier studies. Patients whose tests reveal elevated antibody levels should be monitored closely, they said.

The authors concluded that the new data support the safety of the therapy and align with earlier research.

“These findings add to the wealth of data supporting the long-term safety and efficacy of agalsidase beta in the treatment of Fabry disease,” they concluded.


Tsurumi M, Suzuki S, Hokugo J, Ueda K. Long-term safety and efficacy of agalsidase beta in Japanese patients with Fabry disease: aggregate data from two post-authorization safety studies [published online ahead of print, 2021 Mar 10]. Expert Opin Drug Saf. 2021;1-13. doi:10.1080/14740338.2021.1891221

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