Multiple switches between GP2015, an etanercept biosimilar, with originator product do not impact efficacy, safety and immunogenicity in patients with chronic plaque-type psoriasis: 30-week results from the phase 3, confirmatory EGALITY study

Abstract

Background: EGALITY was a phase III confirmatory efficacy and safety study conducted in patients with plaque-type psoriasis as a part of totality of evidence gathered during the development of GP2015, an etanercept biosimilar.

Objective: To demonstrate equivalent efficacy and comparable safety and immunogenicity of GP2015 and the etanercept originator product (ETN, Enbrel^® ) and evaluate effects of repeated switching between GP2015 and ETN. Results for efficacy, safety and immunogenicity during treatment period (TP) 2 (TP2) are presented pooling the two continued treatment arms (pooled continued) versus the two treatment arms with repeated switches (pooled switched).

Methods: Patients (n = 531) were randomized 1:1 to self-administer GP2015 or ETN twice-weekly subcutaneously during TP1. Patients with a ≥50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were re-randomized for TP2 to continue the same treatment at once-weekly dosing or to undergo three consecutive treatment switches between GP2015 and ETN until week 30. Patients continued the last-assigned treatment during TP2, until week 52.

Results: Mean (standard deviation [SD]) PASI scores at baseline were similar in patients who underwent multiple switches compared to those with continued treatments during TP2. During TP2, PASI 50, PASI 75 and PASI 90 response rates, percent change from baseline in PASI scores and all other efficacy parameters were similar between the pooled switched and pooled continued treatment groups at all time points. The incidence of treatment-emergent adverse events including injection site reactions was comparable between the pooled switched (36.7%) and pooled continued (34.9%) groups. None of the patients in either treatment group were positive for binding anti-drug antibodies in TP2.

Conclusion: Treatment efficacy, safety and immunogenicity were similar between the pooled continued and pooled switched treatments during TP2, indicating that there are no effects in the short term on clinical data of multiple switches between GP2015 and ETN.

Figure 1

Study design. Patients who had achieved at least a 50% improvement in PASI 50 from baseline at week 12 were re‐randomized during treatment period 2 to either continue the same treatment on a once‐weekly dosing schedule, or to undergo a sequence of 3 treatment switches between GP2015 and ETN at 6‐week intervals until week 30. Of the 14 patients who did not enter treatment period 2, 5 patients did not achieve PASI 50 at week 12 (3 others who also did not achieve PASI 50 continued erroneously during treatment period 2); 7 patients discontinued immediately after week 12 (3 patients were not re‐randomized; 4 were re‐randomized but did not take any study drug during treatment period 2); 2 patients achieved PASI 50 at week 12 but had no data beyond week 12. ETN=etanercept originator product

Figure 2

Observed and percent change from baseline in PASI score during TP2 (TP2 per‐protocol set). (a) Observed PASI scores, (b) Percent change in PASI scores. Pooled switched treatment group included patients who switched from treatment with either GP2015 or ETN to treatment sequences ETN>GP2015 > ETN or GP2015 > ETN>GP2015 during treatment period 2, respectively. The pooled continued treatment group included patients who received GP2015 or ETN continuously from treatment period 1. ETN=etanercept originator product; PASI, psoriasis area and severity index; TP2, treatment period 2; SD, standard deviation; W, week.

Figure 3

Adjusted PASI 50, 75 and 90 response rates during TP2 (TP2 per‐protocol set). Pooled switched treatment group included patients who switched from treatment with either GP2015 or ETN to treatment sequences ETN>GP2015 > ETN or GP2015 > ETN>GP2015 during treatment period 2, respectively. The pooled continued treatment group included patients who received GP2015 or ETN continuously from treatment period 1. CI, confidence interval; ETN, etanercept originator product; PASI, psoriasis area and severity index; PPS, per‐protocol set; TP2, treatment period 2; W, week.

Figure 4

Proportion of IGA responders during TP2 (TP2 per‐protocol set). An IGA responder was defined as a patient who achieved a score of 0 (‘clear’) or 1 (‘almost clear’) and improved by at least 2 points on the IGA scale compared with baseline IGA, Investigator's Global Assessment; TP2, treatment period 2; W, week.

Figure 5

Percent change in DLQI overall scores during TP2 (TP2 per‐protocol set). Pooled switched treatment group included patients who switched from treatment with either GP2015 or ETN to treatment sequences ETN>GP2015 > ETN or GP2015 > ETN>GP2015 during treatment period 2, respectively. Pooled continued treatment group included patients who received GP2015 or ETN continuously from treatment period 1. DLQI, Dermatology Life Quality Index; ETN, etanercept originator product; TP2, treatment period 2; W, week.