Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity.

Background Sandoz adalimumab SDZ-ADL (GP-2017) is an approved adalimumab biosimilar with similar efficacy and comparable safety and immunogenicity to reference adalimumab (ref-ADL) as confirmed by analytical, pharmacokinetic and confirmatory studies. ADMYRA, a phase III double-blind study, was conducted with an aim to generate efficacy, safety and immunogenicity comparability data in patients with moderate-to-severe rheumatoid arthritis (RA) having inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). The study also evaluated an aspect of 'switching' reference product to the biosimilar in terms of efficacy, safety and immunogenicity up to Week 48. Methods Eligible patients (N = 353) were randomized 1:1 to receive subcutaneous (sc) SDZ-ADL 40 mg (n = 177) or ref-ADL (n = 176) every other week from Week 0 to Week 24. At Week 24, all patients with at least a moderate response by Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) in the SDZ-ADL group continued SDZ-ADL (n = 159), and in the ref-ADL group were switched to SDZ-ADL (n = 166), treated for up to 46 weeks. The primary endpoint was change in DAS28-CRP from baseline at Week 12. Other efficacy endpoints included proportion of patients with European League Against Rheumatism (EULAR) response, EULAR remission, Boolean remission, safety and immunogenicity. Results The DAS28-CRP score changes from baseline at Week 12 were similar between SDZ-ADL (− 2.16) and ref-ADL (− 2.18) with a mean difference (95% CI) of 0.02 (− 0.24 to 0.27), which was within the pre-specified equivalence margin of ± 0.6. After switching treatment from ref-ADL to SDZ-ADL, the mean DAS28-CRP change was similar between the SDZ-ADL and 'ref-ADL/switched SDZ-ADL' group (− 3.09 vs − 3.05). The proportion of patients with good/moderate EULAR response was 69.2%/29.0% in the SDZ-ADL group and 68.0%/29.6% in the 'ref-ADL/switched SDZ-ADL' group. The proportion of patients in EULAR remission was 51.4% and 54.4% and in Boolean remission was 16.8% and 21.6% for SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups, respectively. The secondary endpoints were similar across the treatment groups. The incidence of adverse events (AEs) and injection-site reactions were low and similar between SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups (AEs 70.6% vs 68.8%, injection-site reactions 4.0% vs 6.3%), and most of these patients experienced AEs of mild or moderate severity. Antidrug antibodies were detected in 24.2% and 25.6% of patients treated with SDZ-ADL and 'ref-ADL/switched SDZ-ADL', respectively, from baseline to Week 48, of which 72.5% in SDZ-ADL and 79.1% in 'ref-ADL/switched SDZ-ADL' groups were neutralizing. Conclusions In patients with moderate-to-severe RA who had an inadequate response to DMARDs, SDZ-ADL demonstrated a similar efficacy and a comparable safety and immunogenicity profile to ref-ADL. Efficacy was sustained after switching from ref-ADL to SDZ-ADL with no impact on safety (NCT02744755).

No abstract

BackgroundSDZ-ADL is approved by EMA in all indications of refADL based on preclinical and clinical study results. EMA submission data included results of a Phase 3 study in patients with plaque psoriasis. ADMYRA was a Phase 3 study comparing efficacy and safety of SDZ-ADL and refADL in patients with moderate-to-severe RA with inadequate response to disease modifying anti-rheumatic drugs, including methotrexate (NCT02744755).ObjectivesThe ADMYRA study was designed to compare the efficacy of SDZ-ADL and refADL over 24 weeks of treatment, and to evaluate long-term efficacy, safety, and immunogenicity of SDZ-ADL up to Week (Wk) 48. The study also investigated the effect of the switch from refADL to SDZ-ADL at Wk 24 on efficacy, safety, and immunogenicity up to Wk 48. This abstract focuses on the data after switch from refADL to SDZ-ADL.MethodsEligible patients were randomized 1:1 to receive 40 mg subcutaneous SDZ-ADL or refADL every other week from Wk 0–22. At Wk 24, patients in the refADL arm were switched to receive SDZ-ADL; treatment continued until Wk 46. The primary endpoint was change in Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) from baseline at Wk 12. Secondary endpoints included mean changes in DAS28-CRP scores, the proportion of patients fulfilling EULAR responses, EULAR and Boolean remission criteria, safety, and immunogenicity. EULAR remission was defined as DAS28-CRP <2.6. Boolean remission was defined as tender joint count 28 ≤1, swollen joint count 28 ≤1, CRP ≤1 mg/dL, and patient global assessment ≤10 on a 100 mm scale.ResultsAs reported previously, mean change in DAS28-CRP from baseline at Wk 12 was -2.16 for SDZ-ADL (N=140) and -2.18 for refADL (N=144).1 Efficacy in both treatment arms was maintained throughout the study, also after the switch from refADL to SDZ-ADL at Wk 24. Mean change in DAS28-CRP from baseline at Wk 48 was -2.90 and -2.92 for refADL/switched and SDZ-ADL groups, respectively. At Wk 48, the proportion of patients with moderate/good EULAR response was 29.6/68.0% in refADL/switched group and 29.0/69.2% in SDZ-ADL group. At Wk 48, the proportion of patients in EULAR remission was 54.4 and 51.4% and in Boolean remission was 21.6 and 16.8% for refADL/switched and SDZ-ADL groups, respectively. As previously reported, safety and immunogenicity were similar in both arms before switch.1 No new safety concerns were identified after switch. After switch, 32.5% of patients in the refADL/switched group and 36.5% of patients in the SDZ-ADL group experienced adverse events (AEs); serious AEs were reported by 3.6 and 2.5%, respectively. The proportion of patients reporting injection site reactions after switch was 1.2% in the refADL/switched group and 0.6% in the SDZ-ADL group, respectively. After switch, 26.3 and 24.0% of patients were positive for antidrug antibodies (ADAs) in refADL/switched and SDZ-ADL groups, respectively. Of these, 81.0 vs 72.2% were neutralizing. ADA positivity had no clinically meaningful impact on safety.ConclusionAfter the switch...

No abstract