JCR Launches the First Biosimilar Agalsidase Beta

JCR Pharmaceuticals announced yesterday that it has launched its biosimilar agalsidase beta product, referencing Fabrazyme, in Japan for the treatment of the lysosomal storage disorder (LSD) Fabry disease (FD). JCR developed the drug in partnership with Amicus Therapeutics and GlaxoSmithKline.

The product, Agalsidase Beta BS IV Infusion, which will be available in 5-mg and 35-mg vials, was approved by Japan’s Ministry of Health, Labor, and Welfare in September 2018. In its announcement of the product’s availability, JCR noted that not only is the product the first biosimilar agalsidase beta, it is also the first product for the treatment of an LSD that will be produced domestically in Japan.

Japanese regulators approved the product on the basis of a data package that included findings from a nonclinical evaluation of the product in comparison with its reference that determined that the amino acid sequence of the products was identical. A higher-order assessment of the structures revealed both molecules to have similar structural properties and comparable enzyme activity. The biosimilar had a similar glycosylation profile to the reference, but the biosimilar demonstrated slightly better cellular uptake of enzymes than the reference did (this fact did not affect pharmacokinetics of efficacy, however).

Like its reference, the biosimilar product is a recombinant human alpha-galactosidase A enzyme replacement therapy for FD, which is a rare inherited disorder that affects 1 in 40,000 to 60,000 men. (While FD can also affect women, its prevalence in female patients is not known.) FD stems from a mutation in the alpha-galactosidase A gene that causes a buildup of globotriaosylceramide in cells. This buildup can adversely affect the functioning of the heart, kidneys, and other organs and lead to cardiac disease, stroke, renal failure, and early death.

Given how critical treatment with agalsidase beta is to control FD, the availability of a biosimilar option will be welcome to patients, who in the past have faced shortages of the reference Fabrazyme. In 2009, a manufacturing process introduced viral contamination into the Sanofi Genzyme reference drug, sparking a global shortage of this crucial therapy.

During the shortage, patients were instructed by the European Medicines Agency to reduce their dosages, but after an increased rate of serious adverse events was observed among FD patients who followed directions to reduce their doses, patients were subsequently asked to switch to other treatment options. In the United States, patients with FD unsuccessfully petitioned the US government to force Sanofi Genzyme to license its patent for Fabrazyme to biosimilar developers in order to create further supply of the treatment.

To date, JCR has not announced whether it will seek European or US regulatory authorization for the biosimilar.