Fabrazyme Biosimilar JR-051 Seen As Safe, Effective in Preclinical Animal Study

In a preclinical animal study, JCR Pharmaceuticals’ biosimilar candidate JR-051 was seen to be as effective as the approved therapy Fabrazyme (agalsidase beta) at reducing levels of globotriaosylceramide (Gb3), a fat molecule that accumulates in Fabry disease.

The study’s results add to previous Phase 2/3 clinical data and suggest that JR-051 could become an available therapy for Fabry disease.

The preclinical study, “Non-clinical evaluation of JR-051 as a biosimilar to agalsidase beta for the treatment of Fabry disease,” was recently published in the journal Molecular Genetics and Metabolism.

Fabry disease is a storage disorder caused by mutations in the α-galactosidase A (GLA) gene that result in absent or markedly reduced GLA enzymatic activity. This leads to the damaging accumulation of two fat molecules — Gb3 and lysoGb3 — in tissues such as the heart, kidneys, nervous system, eyes, and skin.

Enzyme replacement therapy replaces the faulty GLA enzyme and restores its normal function. Currently, two versions of the enzyme exist — agalsidase beta (or Fabrazyme, developed by Sanofi Genzyme) and agalsidase alpha (or Replagal, developed by Shire) — but only Fabrazyme is approved by the U.S. Food and Drug Administration.

The emergence of agalsidase beta biosimilars has the potential to reduce the treatment’s high cost and to prevent or mitigate the effects of any future shortages of Fabrazyme for this underserved patient population. A biosimilar is a biological medicine with a high degree of similarity to an already approved biological medicine in terms of quality, safety, and efficacy.

JR-051 was developed in Japan by JCR Pharmaceuticals in collaboration with Amicus Therapeutics and GlaxoSmithKline as a biosimilar to Fabrazyme. It is produced using Chinese hamster ovary cells without animal-derived raw materials.

Researchers from JCR Pharmaceuticals compared JR-051 to Fabrazyme in terms of pharmacokinetics, safety, and therapeutic effects. They used cells cultured in the lab, healthy rats, non-human primates, and a mouse model of Fabry disease. Pharmacokinetics refer to a drug’s absorption, bioavailability, distribution, metabolism, and excretion in the body.

JR-051’s molecular structure and enzyme activity were similar to Fabrazyme’s. JR-051 and Fabrazyme were processed by the body in similar ways in all animals tested.

In mice, JR-051 reduced Gb3 levels in the kidney, skin, liver, spleen, heart, and blood as efficiently as Fabrazyme. The compound also was seen as safe in a 13-week evaluation in non-human primates.

Earlier this year, JCR Pharmaceuticals announced the results of a multicenter, open-label, Phase 2/3 study in Japan that compared the safety profile and efficiency of JR-051 with Fabrazyme in 16 Fabry patients. JR-051 had a similar safety profile as Fabrazyme and was effective at reducing blood levels of Gb3 and lysoGb3.

Preclinical and clinical data supported the company’s submission to Japan’s Health Ministry of a marketing authorization application for JR-051 to treat Fabry disease.