A Phase 3 Randomized, Double-blinded, Active-controlled, Multicenter Trial to Evaluate the Safety and Efficacy of Fabagal® (Agalsidase Beta) in Patients With Fabry Disease

Evaluate the safety and efficacy of Fabagal® developed by ISU ABXIS Co., Ltd., which has similar efficacy to active comparator (Agalsidase beta).

Start Date14 Apr 2023

Sponsor / Collaborator

ISU Abxis Co., Ltd.

100 Clinical Results associated with Agalsidase beta biosimilar(ISU Abxis Co., Ltd.)

100 Translational Medicine associated with Agalsidase beta biosimilar(ISU Abxis Co., Ltd.)

100 Patents (Medical) associated with Agalsidase beta biosimilar(ISU Abxis Co., Ltd.)

Literatures (Medical) associated with Agalsidase beta biosimilar(ISU Abxis Co., Ltd.)

01 Dec 2024·Molecular Genetics and Metabolism Reports

Comparative pharmacokinetics and pharmacodynamics of two formulations of agalsidase beta (agalsidase Biosidus) and Fabrazyme® by intravenous infusion in healthy male volunteers

Article

Author: Salgueiro, Natali D ; Dome, Laila ; Coppola, Sabrina ; Gobbi, M. Gabriela ; Diez, Roberto A ; Pirotzky, Eduardo M. ; Taconelli, Hernán D ; Beider, Lara ; Taconelli, Hernán D. ; Sotelo, Hugo ; Diez, Roberto A. ; Salgueiro, Natali D. ; Pirotzky, Eduardo M ; Gobbi, M Gabriela ; Berstein, Viridiana

Fabry disease is a rare X-linked lysosomal condition that leads to the accumulation of glycosphingolipids in various tissues, causing cellular dysfunction, tissue remodeling, progressive fibrosis, and organ failure. The disease results from a deficiency in the human α-galactosidase A enzyme, responsible for breaking down glycosphingolipids like globotriaosylceramide (GL-3 or Gb3) into galactose and dihexose ceramides. In individuals diagnosed with Fabry disease, treatment from 2 years of age onwards typically involves agalsidase beta, the normal recombinant form of the defective enzyme. Agalsidase beta from Biosidus has been developed as a biosimilar to Sanofi-Genzyme's Fabrazyme®. In the molecule's clinical journey, a phase I trial was designed to establish its similarity in terms of pharmacokinetics, pharmacodynamics, and immunogenicity compared to the reference medication. The study was conducted on 24 healthy male volunteers, aged between 18 and 40 years. All volunteers received a single 1 mg/kg bw dose of Fabrazyme® or Biosidus Agalsidase beta by continuous intravenous (IV) infusion over 5 h. The 90 % confidence interval (CI) of the maximum concentration (Cmax), area under the plasma concentration-time curve from time 0 to 12 h (AUC0-12 h) and area under the plasma concentration-time curve extrapolated from time 0 to infinity (AUC0-∞) ratios fell within the accepted range of 80-125 %. No differences were detected in adverse effects or antibody induction. This indicates that Biosidus agalsidase beta meets the criteria for being considered similar to the reference formulation Sanofi Genzyme's Fabrazyme®.

01 Sep 2024·Molecular Genetics and Metabolism Reports

Comparative study on incorporation of three recombinant human α-galactosidase A drugs (agalsidases) into cultured fibroblasts and organs/tissues of Fabry mice

Article

Author: Sakuraba, Hitoshi ; Togawa, Tadayasu ; Shiga, Tomoko ; Tsukimura, Takahiro

Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A (α-Gal A) drugs (agalsidases) has been successfully used for treatment of Fabry disease, and three kinds of agalsidases are now available in Japan. To compare the biochemical characteristics of these drugs, especially focusing on their incorporation into cultured fibroblasts and organs/tissues of Fabry mice, we performed in vitro, cell, and animal experiments. The results revealed that there were no differences in the kinetic parameters and enzyme activity between these agalsidases. But their affinity for domain 9 of cation-independent mannose 6-phosphate receptor (CI-M6PR), which exists in various cells, was higher in the order: agalsidase beta biosimilar 1 (agalsidase beta BS) > agalsidase beta > agalsidase alfa, which almost coincided with the experimental results regarding the efficiency of their incorporation into cultured fibroblasts derived from a Fabry mouse. The results of animal experiments using Fabry mice revealed that the incorporation of the agalsidases into the kidneys and heart, where CI-M6PRs are widely distributed, was efficient in the order: agalsidase beta/agalsidase beta BS > agalsidase alfa, which reflected the degree of reduction of glycosphingolipids accumulated in the organs/tissues. On the other hand, no differences in the efficiency of their uptake or reduction of the accumulated substances were observed in the liver, probably due to asialoglycoprotein receptors expressed on the surface of hepatocytes. This information will be useful for making a suitable ERT plan for individual Fabry patients with various backgrounds and for developing new ERT drugs in the future.

16 Sep 2022·Medicine

A phase II, multicenter, open-label trial to evaluate the safety and efficacy of ISU303 (Agalsidase beta) in patients with Fabry disease

Article

Author: Lee, Chang Hwa ; Choi, Yunha ; Kim, Dae-Seong ; Yoo, Han-Wook ; Hwang, Soojin ; Kim, Woo-Shik ; Lee, Beom Hee ; Choi, Jin-Ho ; Kim, Ja Hye ; Cheon, Chong Kun

Background:Fabry disease (FD) is caused by a deficiency in the activity of the lysosomal enzyme, α-galactosidase A (α-Gal A), which leads to globotriaosylceramide (Gb3) deposition in multiple tissues. The current management of FD is enzyme replacement therapy (ERT). We report on the efficacy and safety of a new agalsidase beta, ISU303, in FD.Methods:Ten patients (7 males, 3 females) were enrolled and administered a 1 mg/kg dose of ISU303, every other week for 6 months. The primary endpoint was the normalization of plasma Gb3 level. The secondary endpoints were the changes from baseline in urine Gb3 and the plasma and urine lyso-globotriaosylsphingosine (lyso-Gb3) level. Echocardiography, renal function test, and pain-related quality of life were also assessed before and after administration. Safety evaluation was performed including vital signs, laboratory tests, electrocardiograms, antibody screening tests, and adverse events at each visit.Results:At 22 weeks of treatment, plasma and urine Gb3 level decreased by a mean of 4.01 ± 1.29 μg/mL (range 2.50–5.70) (P = .005) and 1.12 ± 1.98 μg/mg Cr. (range 0.04–5.65) (P = .017), respectively. However, no significant difference was observed in plasma and urine lyso-Gb3 levels. Echocardiography also was not changed. Renal function and pain-related quality of life showed improvements, but there was no clinical significance. No severe adverse events were observed. Only 1 patient developed an anti-drug antibody without neutralizing activity during the trial.Conclusion:This study showed the efficacy and safety of ISU303. Treatment with ISU303 significantly resulted in plasma and urine Gb3 decrease in patients with FD. These results suggest that ISU303 is safe and effective and can alternative ERT for FD.

100 Deals associated with Agalsidase beta biosimilar(ISU Abxis Co., Ltd.)

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R&D Status

Approved

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Indication	Country/Location	Organization	Date
Fabry Disease	KR	ISU Abxis Co., Ltd.	07 Jan 2014

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Fabry Disease	Phase 3	PH	ISU Abxis Co., Ltd.	14 Apr 2023

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