Tocilizumab Biosimilars Show Similar Safety, Tolerability, Immunogenicity to Reference: ACR Abstracts

Two tocilizumab biosimilars had similar safety, tolerability, and immunogenicity compared with the reference biologic, according to abstracts presented at the American College of Rheumatology (ACR) annual meeting. One biosimilar, MSB11456, was a proposed product being tested in healthy adults, while the other, BAT1806 (also known as BIIB800), had results from a phase 3 trial.

The FDA recently accepted Biogen’s biologics license application for BIIB800 for review. The European Medicines Agency accepted Biogen’s marketing authorization application for BIIB800 for review in September 2022.

The phase 3, randomized, double-blind, active-controlled trial of BAT1806 was conducted in 55 sites in China and Central Europe. The abstract presented at ACR reported on results from weeks 24 to 48 of the trial.¹ Patients were randomized to 3 groups: (1) BAT1806 up to week 48 (n = 290), (2) the reference up to week 48 (n = 142), or (3) the reference up to week 24 (n = 145) followed by the biosimilar from weeks 24 to 48.

At week 48, 90.4% of patients in group 1 had a 20% improvement in ACR response criteria (ACR20), 90.3% in group 2 were ACR20 responders, and 87.8% of patients in group 3 were ACR20 responders.

Patients on the biosimilar through week 48 had the lowest levels of treatment-emergency adverse events (TEAEs):

• 55.9% in group 1, 62.1% in group 2, and 64.8% in group 3 had any TEAE:
  • 38.6% in group 1, 40.7% in group 2, and 45.1% in group 3 had a TEAE that was treatment related
• 2.8% in group 1, 2.8% in group 2, and 3.5% in group 3 had a serious TEAE:
  • 0.7% in all 3 groups had a serious TEAE related to treatment
• There were no deaths reported
• Antidrug antibodies were reported in 21.0% in group 1, 18.6% in group 2, and 16.2% in group 3
• Neutralizing antibodies were present in 21.0% in group 1, 17.9% in group 2, and 16.2% in group 3
• Geometric mean trough serum concentrations were comparable for the 3 treatment groups

Throughout the treatment period of the study, the efficacy, safety, immunogenicity, and pharmacokinetic (PK) profiles were comparable between the 3 groups of patients, the researchers concluded.

In the study of a proposed tocilizumab biosimilar in healthy adults, MSB11456’s PK, safety, tolerability, and immunogenicity profiles were compared with the reference in a randomized, double-blind, parallel-group single-dose study.²

A total of 128 participants received either the biosimilar (n = 62) or the reference product (n = 66). Participants received a single intravenous infusion of 8 mg/kg of the biosimilar or the reference.

The analysis found equivalence between the biosimilar and reference product with 90% CI for the geometric least-squares mean ratios area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration (AUC0-last) entirely contained with the 80% to 125% equivalence limits.

Overall, the study demonstrated PK equivalence with similar safety, tolerability, and immunogenicity between the 2 products. The results support the proposed biosimilar to reference tocilizumab, the researchers concluded.

Reference

1. Leng X, Leszczynski P, Jeka S, et al. Fifty-two-week results from a phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a proposed tocilizumab biosimilar, with a tocilizumab reference product in subjects with moderate to severe RA with an inadequate response to methotrexate. Presented at: ACR Convergence 2022; November 10-14, 2022; Philadelphia, PA. Abstract 0917.

2. Tomaszewska-Kiecana M, Ullmann M, Vincent E, Petit-frere C, Monnet J, Illes A. Pharmacokinetics, safety, tolerability, and immunogenicity of a proposed tocilizumab biosimilar (MSB11456) versus US‑licensed tocilizumab: results of a randomized, double-blind, parallel‑group, single‑intravenous dose study in healthy adults (APTURA II). Presented at: ACR Convergence 2022; November 10-14, 2022; Philadelphia, PA. Abstract 1421.