Abstracts from the 2022 European Hematology Association (EHA) Congress presented positive data for 2 biosimilar candidates referencing Soliris (eculizumab).
Abstracts from the 2022 European Hematology Association (EHA) Congress presented positive data for 2 biosimilar candidates referencing Soliris (eculizumab): Amgen’s ABP 959 and Samsung Bioepis’ SB12.
Eculizumab is a humanized recombinant IgG2/4k monoclonal antibody that is used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optical spectrum disorder.
Phase 1 PD and PK Similarity of ABP 959 vs Soliris
For the first abstract,1 researchers conducted a phase 1, randomized, double-blind, single-dose, 3-arm, parallel-group trial with 219 healthy adult male subjects aged 18 to 45 years. For inclusion, the participants had to have a body mass index of 18.0 to 30.0 kg/m2. They were randomized to receive a 300-mg intravenous infusion of ABP 959 or the reference product, either the US version or the EU version.
Serum samples were collected over 56 days to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the biosimilar vs the reference product. The primary end points were evaluated by area under the total serum concentration vs time curve (AUC) from time 9 extrapolated to infinity (AUCinf) and an area between the effect curve (ABEC) of 50% total hemolytic complement activity (CH50).
After randomization, 71 participants were given the biosimilar, 74 were given the US Soliris, and 74 were administered the EU Soliris. The prespecified equivalence criterion for PK and PD evaluation is a 95% CI for geometric means (GM) ratio between 0.80 and 1.25.
The results revealed that the GM of AUCinf for unbound eculizumab was 5072.1 h.mcg/mL for ABP 959, 5527.6 h.mcg/mL for eculizumab US, and 5070.3 h.mcg/mL for eculizumab EU. The GM of ABEC of CH50 was 17,724.5 for APB 959, 16,549.4 for the US reference product, and 16,361.1 for the EU reference product. Overall, the resulting 90% and 95% CIs of GM ratios were found to be within the criteria to establish bioequivalence.
Phase 3 Comparison Between SB12 and Soliris
Data from a phase 3, randomized, double-blind, multicenter, cross-over study comparing SB12 with Soliris in patients with PNH were also shared at the meeting.2 The study evaluated the clinical efficacy, safety, PK, PD, and immunogenicity of the biosimilar vs the reference product.
Overall, 50 patients with PNH who (1) were at least 18 years old, (2) had lactate dehydrogenase (LDH) levels within 1.5 of the upper limit of normal, and (3) did not have previous exposure to a complement inhibitor were enrolled in the analysis. The patients were randomized 1:1 to the treatment group 1, where patients started treatment on the biosimilar and switch to the originator (n = 25), or treatment group 2, where patients started using the originator and switched to the biosimilar (n = 25).
Patients received a 600-mg intravenous dose weekly of the first drug in the treatment group for 4 weeks and 900 mg for the fifth week, followed by 900-mg doses administered every 2 weeks until week 26, when patients were switched to receive the second drug. The patients would remain on the second drug until week 50.
In total, 49 patients received treatment with a study drug and 46 completed the full 50 weeks. The mean difference in LDH level measured at week 26 between the biosimilar and the reference product was 34.48 (95% CI, –47.66 to 116.62).