A phase III, randomised, double-blind, multi-national clinical trial comparing SB12 (proposed eculizumab biosimilar) and reference eculizumab in patients with paroxysmal nocturnal haemoglobinuria.

Autor: Jang JH; Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea., Gomez RD; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico., Bumbea H; Bucharest Emergency University Hospital Bucharest Romania., Nogaieva L; Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council Cherkasy Ukraine., Wong LLL; Queen Elizabeth Hospital Kota Kinabalu Malaysia., Lim SM; Sultanah Aminah Hospital Johor Bahru Malaysia., Kim Y; Samsung Bioepis Incheon Republic of Korea., Park J; Samsung Bioepis Incheon Republic of Korea.
Jazyk: angličtina
Zdroj: EJHaem [EJHaem] 2022 Dec 20; Vol. 4 (1), pp. 26-36. Date of Electronic Publication: 2022 Dec 20 (Print Publication: 2023).
DOI: 10.1002/jha2.632
Abstrakt: Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross-over at week 26). Primary endpoints were LDH at week 26 and the time-adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] -47·66‒116·62 U/l) and geometric LSM ratio of time-adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre-defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti-drug antibodies. Treatment-emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12-use in PNH patients.
Competing Interests: Roberta Demichelis Gomez has received speaker honoraria from Abbvie, Amgen, and Astellas, meeting support from Abbvie, research awards from American Society of Hematology (ASH), and participated in data safety monitoring or advisory boards of Abbvie, Amgen, Astellas, Gilead, and Teva. Horia Bumbea received speaker honoraria from Janssen, Roche, Abbvie, Novartis, Novonordisk, Sandoz, Alvogen, Amgen, Accord, Genesis, Angellini, Takeda, Bristol‐Meyers‐Squibb, Sanofi, and AstraZeneca, meeting support from Janssen, Roche, Abbvie, Novartis, Sandoz, Alvogen, Amgen, Accord, Genesis, Angellini, Takeda, Bristol‐Meyers‐Squibb, and Sobi, and participated in data safety monitoring or advisory boards of Janssen, Roche, Abbvie, Novartis, Novonordisk, Sandoz, Alvogen, Amgen, Accord, Genesis, Angellini, Takeda, Bristol‐Meyers‐Squibb, and AstraZeneca. Younsoo Kim and Jihye Park are employees of Samsung Bioepis. Jun Ho Jang, Larysa Nogaieva, Lily Lee Lee Wong, and Soo Min Lim declared no competing interests.
(© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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