A RANDOMIZED, DOUBLE-BLIND, PHASE 3 EQUIVALENCE TRIAL COMPARING THE ETANERCEPT BIOSIMILAR, HD203, WITH ENBREL (R), IN COMBINATION WITH METHOTREXATE (MTX) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA)

Abstract

Background Etanercept is a recombinant fusion protein that blocks TNF activity. HD203 is a biosimilar of etanercept. In a double-blind, randomized study in healthy volunteers, HD203 and Enbrel® were comparable with regards to pharmacokinetics, safety and tolerability.

Objectives To evaluate the equivalence in efficacy and to compare the safety of HD203 (biosimilar etanercept) and Enbrel® (reference etanercept), in combination with MTX in patients with RA. (ClinicalTrials.gov identifier NCT01270997).

Methods Patients (male or female aged ≥20 years) with active RA were randomly assigned (1:1) to25 mg HD203 or Enbrel®, administered subcutaneously twice weekly with MTX for 48 weeks. The primary endpoint was the proportion of patients achieving ACR20 at week 24. Secondary endpoints included ACRn, change in DAS28, and EULAR response at week 24 and 48, safety and immunogenicity. Efficacy and safety were evaluated at screening, week 0, 2, 4, 8, 12, 16, 20, and 24. Immunogenicity, efficacy and safety were also evaluated at week 36 and 48.

Results In total, 294 patients were randomized: 147 to HD203 and 147 to Enbrel®. The proportion of patients achieving ACR20 at week 24 (primary endpoint) was not significantly different for HD203 and Enbrel® (Table) and equivalence in efficacy was demonstrated within predefined margins. In addition, there were no statistically significant differences between proportions achieving ACR20 at weeks 12 and 48. Similar trends were seen for ACR50 and ACR70, however the proportion of patients achieving ACR50 at week 24 and 48 was higher with HD203 than with Enbrel®. There were no statistically significant differences between the groups for ACRn, change in DAS28, and EULAR response at week 24 and 48.