A Randomized, Double-Blind, 2-Treatment, 2-Period, Crossover Phase 1 Study to Compare the Pharmacokinetics, Safety and Tolerability of 60 IU/Kg of Abcertin and Cerezyme in Healthy Volunteers Following a Single Intravenous Administration.
Eungu Kang, Dohyung Kim, Soojin Hwang, Charlotte Lemech, Jessica Wharton, Yongyoon Lee, Han Wook Yoo, Beom Hee Lee
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引用次数: 0
Abstract
Background: Imiglucerase (Cerezyme; Sanofi, Paris, France), an analogue of β-glucocerebrosidase produced by recombinant DNA technology, has been a safe and effective treatment for Gaucher disease (GD) for over 25 years. A new imiglucerase, Abcertin (Seongnam-si, Gyeonggi-do, Republic of Korea) has shown a similar safety and efficacy profile in previous clinical studies. This study compared the pharmacokinetics, immunogenicity, safety, and tolerability to EU-sourced Cerezyme following a single 60 IU/kg dose.
Methods: This phase 1, single-center, randomized, double-blind, two-way crossover study enrolled 36 healthy volunteers aged 18-45 years. Participants were randomly assigned to receive either Abcertin or Cerezyme in a predetermined sequence.
Results: Abcertin reached peak plasma concentrations at a median tmax of 61 min (range: 40-121 min). The mean Cmax, AUC0-last, and AUC0-inf were 115.4 mU/mL, 12,190 min·mU/mL, and 12,210 min mU/mL, respectively, indicating bioequivalence to Cerezyme. The mean t½, CL, and Vz were 6.88 min, 376.7 mL/min, and 3.62 L, respectively, and were comparable between the two treatments. One participant in the Cerezyme group developed anti-drug antibodies, which were non-neutralizing A total of 24 subjects experienced treatment-emergent adverse event (TEAE). The most common TEAE was headache (3 in the Abcertin group and 5 in the Cerezyme group), followed by general disorders and administration site condition (3 in Abcertin group and 5 in Cerezyme group). Two participants in the Cerezyme sequence experienced severe TEAEs: one had a urinary tract infection, and the other developed urticaria, which leading to study withdrawal.
Conclusion: Abcertin demonstrated pharmacokinetic equivalence to Cerezyme, with a comparable safety, immunogenicity, and tolerability profile. These findings support its potential as an affordable biosimilar for GD treatment.
期刊介绍：
Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care.
Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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