(27) Clinical similarity of eculizumab-aeeb (BKEMV, Amgen) and eculizumab reference product in patients with PNH supports interchangeability designation

Background: : Eculizumab-aeeb (BKEMV®, ABP 959) is a biosimilar to eculizumab reference product (RP). Eculizumab is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optical spectrum disorder. Regulatory approval of biosimilars is based on the totality of evidence, which includes demonstration of similarity in analytical and non-clinical characteristics, and comparative clinical studies.

Objective: : To report the primary efficacy results from the clinical comparability study in patients with PNH to support the demonstration of similarity of ABP 959 with RP.

Methods: : A multicenter, randomized, double-blind, active-controlled, 2-period crossover study evaluated the clinical similarity of ABP 959 compared with RP in adults with PNH. Patients stable on RP (>6 months) were randomized 1:1 to receive each investigational product (900 mg of ABP 959 or RP IV q14d) in 1 of 2 treatment sequences (ABP 959/RP or RP/ABP 959). Primary efficacy determined by hemolysis, measured by lactate dehydrogenase (LDH), was analyzed for both parallel and crossover comparisons. Pharmacokinetics (PK) were secondary endpoints.

Results: : Forty-two patients (20 in ABP 959/RP; 22 in RP/ABP 959) were randomized across 25 centers. Similarity of efficacy was established. In the parallel comparison, the ratio of the geometric least squares means of LDH at week 27 (ABP 959 vs RP) was 1.0628, with a 1-sided 97.5% upper confidence interval (CI) of 1.1576 which was contained within the non-inferiority margin of 2.873. In the crossover comparison, a point estimate of the geometric mean ratio (GMR) of time-adjusted area under the effect curve of LDH (ABP 959 vs RP) of 0.9812 with a 2-sided 90% CI of (0.9403-1.0239) was contained within the prespecified similarity margin. The GMR (90% CI) for total and unbound PK area under the curve from week 13 to week 15 was 0.9122 (0.7586, 1.0968) and 0.9508 (0.7454, 1.2130), respectively. Geometric mean values for trough total and unbound concentrations were similar between treatment groups.

Conclusions: : Similarity in clinical efficacy in both parallel and crossover comparisons was established between ABP 959 and RP in adults with PNH. These results, along with previous analytical, non-clinical, clinical PK/PD in healthy adults, and efficacy and safety evaluations in adults with PNH, support a demonstration of no clinically meaningful differences and the interchangeability designation between ABP 959 (eculizumab-aeeb) and RP.

Sponsorship:: Amgen