SB12 (eculizumab-aagh), a biosimilar referencing Soliris (ECU-RP, eculizumab reference product) was approved by FDA under the name Epysqli® for paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, and acetylcholine receptor antibody positive generalized myasthenia gravis (gMG). We report the results of comparability studies of SB12.

SB12 is a recombinant humanized monoclonal antibody that binds to the complement C5 with high affinity. By blocking C5, it prevents cell damage caused by complement-mediated inflammation.

Totality-of-the-evidence of SB12 was provided through i) extensive analytical assessments by more than 40 state-of-the-art assays in terms of structural, physicochemical, biophysical and biological attributes; ii) a Phase 1, randomized, double-blind, single-dose comparative pharmacokinetic (PK) study comparing SB12 with ECU-RP in healthy volunteers; and iii) a Phase 3, randomized, double-blind, multi-national study comparing SB12 and ECU-RP in patients with PNH.

The overall characterization results demonstrated similarity of SB12 to ECU-RP manufactured in the EU and US. In terms of mechanism of action-related biological activities, the % relative binding activity of C5 and % relative potency of C5 inhibition as minimum-maximum [SD] were 99-103 [2.1] and 95-98 [1.5] for SB12; 96-102 [3.2] and 92-96 [2.3] for EU-RP; 100-108 [4.0] and 92-104 [6.4] for US-RP, respectively. In the Phase 1 study, the 90% confidence intervals (CIs) of the geometric least squared means (LSM) ratios of the PK endpoints assessed by AUC_inf, AUC_last and C_max were contained within the bioequivalence margin of 80-125%. In the Phase 3 study, the LSM difference in LDH at week 26 (34.48; 95% CI -47.66-116.62 U/L) and geometric LSM ratio of time-adjusted area under the effect curve of LDH (1.08; 90% CI 0.95-1.23) were within pre-defined equivalence margins.

Comprehensive analytical and clinical studies of SB12 compared to ECU-RP support its use for gMG. Further clinical studies in gMG could provide valuable insight in the treatment.