Non-clinical evaluation of JR-051 as a biosimilar to agalsidase beta for the treatment of Fabry disease

October 11, 2018


Non-clinical evaluation of JR-051 as a biosimilar to agalsidase beta for the treatment of Fabry disease


Hideto Morimoto, Yae Ito, Eiji Yoden, Masato Horie, Noboru Tanaka, Yoshikazu Komurasaki, Ryuji Yamamoto, Kazutoshi Mihara, Kohtaro Minami, Tohru Hirato




Molecular Genetics and Metabolism


Fabry disease (FD) is an X-linked lysosomal storage disease. It is caused by deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to excessive deposition of neutral glycosphingolipids, especially globotriaosylceramide (GL-3), in cells throughout the body. Progressive accumulation of GL-3 causes life-threatening complications in several tissues and organs, including the vasculature, heart, and kidney. Currently available enzyme replacement therapy for FD employs recombinantα-Gal A in two formulations, namely agalsidase alfa and agalsidase beta. Here, we evaluated JR-051 as a biosimilar to agalsidase beta in a non-clinical study. JR-051 was shown to have identical primary and similar higher-order structures to agalsidase beta. Mannose-6-phosphate content was higher in JR-051 than in agalsidase beta, which probably accounts for a slightly better uptake into fibroblasts in vitro. In spite of these differences in in vitro biological features, pharmacokinetic profiles of the two compounds in mice, rats, and monkeys were similar. The ability to reduce GL-3 accumulation in the kidney, heart, skin, liver, spleen, and plasma of Gla-knockout mice, a model of FD, was not different between JR-051 and agalsidase beta. Furthermore, we identified no safety concerns regarding JR-051 in a 13-week evaluation using cynomolgus monkeys. These findings indicate that JR-051 is similar to agalsidase beta in terms of physicochemical and biological properties.




Circular dichroism, Secondary structure, Higher order structure, Tertiary structure, Biochemistry