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Background SDZ-ADL (GP2017; Sandoz GmbH, Austria) is an EMA-/FDA-approved adalimumab biosimilar. The effect of SDZ-ADL on quality of life (QoL) and patient-reported outcomes (PROs) was assessed as part of two phase III studies, one in patients with moderate‐to‐severe chronic plaque psoriasis (PsO; ADACCESS) and the other in patients with rheumatoid arthritis (RA; ADMYRA). Additionally, ADACCESS included patients with psoriatic arthritis (PsA). Methods ADACCESS included 465 patients with PsO, whereas ADMYRA included 353 patients with RA. Both studies evaluated and confirmed equivalent efficacy, similar safety, and immunogenicity of SDZ-ADL with reference adalimumab (ref-ADL). A third of patients underwent multiple (four) treatment switches between study treatments starting at Week 17 (ADACCESS); all patients switched from ref-ADL to SDZ-ADL at Week 24 (ADMYRA). Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in ADACCESS, Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue) score in ADMYRA, and Health Assessment Questionnaire–Disability Index (HAQ-DI) in both studies. Results In both studies, baseline scores for all PRO assessments were comparable between the two treatment groups. In ADACCESS, mean DLQI decreased from baseline in both groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at Week 17 (SDZ-ADL, − 64.5 [80.3]; ref-ADL, − 70.6 [41.7]), which were sustained after the switch at Week 51 (‘continued SDZ-ADL,’ − 79.7 [36.2]; ‘continued ref-ADL,’ − 80.8 [44.6]; ‘switched to SDZ-ADL,’ − 70.7 [32.2]; ‘switched to ref-ADL,’ − 69.3 [49.6]). In ADACCESS, the proportion of patients with an EQ-5D-5L score of 1 (no problems) increased from baseline for all five dimensions in all treatment groups and was comparable between treatment groups at Week 51. In ADACCESS, in patients with PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline in both treatment groups, and scores were comparable between groups at Week 17 (SDZ-ADL, 0.5 [0.6]; ref-ADL, 0.5 [0.6]) and after switching at Week 51 (‘continued SDZ-ADL,’ 0.4 [0.5]; ‘continued ref-ADL,’ 0.4 [0.6]; ‘switched to SDZ-ADL,’ 0.5 [0.8]; ‘switched to ref-ADL,’ 0.7 [0.6]). In ADMYRA, proportion of patients achieving HAQ-DI in the normal range (≤ 0.5) was comparable between treatment groups at Week 24 (SDZ-ADL, 37.8%; ref-ADL, 36.3%) and after switching at Week 48 (‘SDZ-ADL,’ 41.6%; ‘ref-ADL/switched to SDZ-ADL,’ 40.0%). In ADMYRA, mean FACIT-Fatigue scores increased from baseline in both treatment groups. At Week 24, mean (SD) percent change from baseline in the FACIT-Fatigue scores was 75.4 (135.5) in SDZ-ADL and 73.0 (96.3) in ref-ADL groups; the scores were sustained after switching at Week 48. Conclusion Treatment with SDZ-ADL and ref-ADL resulted in comparable improvements in PROs as well as QoL scores across the three diseases, PsO, PsA, and RA. Switching between SDZ-ADL and ref-ADL had no negative impact on PROs across the reported period. Clinical trials.gov identifier NCT02744755, NCT02016105. Supplementary Information The online version of this article (10.1007/s40259-021-00470-1) contains supplementary material, which is available to authorized users.

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). Electronic supplementary material The online version of this article (10.1007/s40259-020-00447-6) contains supplementary material, which is available to authorized users.

Introduction: Antidrug antibody (ADA) development is known to occur with adalimumab treatment and impacts adalimumab exposure. Here, we compare the impact of immunogenicity on pharmacokinetics (PK) across two randomized PK studies of GP2017, an approved biosimilar adalimumab, in healthy subjects. Methods: Healthy male subjects (N= 107 in study GP17-104; N= 90 in study GP17-103) received a single 40 mg subcutaneous injection of the same GP2017 drug product batch. Cross-study PK comparison was performed for log-transformed Cmax, AUC0–360h, AUC0–last, and AUC0–inf, using an ANCOVA model. Results: The proportion of ADA-positive subjects was higher in GP17-103 (in total 71.1%) vs. GP17-104 (57.9%). Comparison of GP2017 PK between studies showed that the exposure was lower in GP17-103 vs GP17-104, with 90% confidence intervals (CIs) for geometric mean ratios of AUC0–last and AUC0–inf being outside the range of 0.80–1.25. A subgroup analysis showed that in ADA-negative subjects 90% CIs for all PK parameters were within range, with geometric mean ratios close to 1.00. Conclusion: The differences in GP2017 PK between the two groups are not considered to be product-related, but may be due to currently unknown factors related to differences between the two study populations.

Background: To compare the pharmacokinetics of Sandoz biosimilar adalimumab (GP2017) with reference adalimumab (Humira) in healthy volunteers (PK similarity study) and to compare the pharmacokineti...

Background SDZ-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). Objectives The 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. Methods Eligible 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 Results As 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. Conclusion After the switch from reference to biosimilar, the rates of EULAR remission/response and Boolean remission were high and maintained until Week 48. Treatment switch from refADL to SDZ-ADL at Wk 24 did not impact efficacy, safety, or immunogenicity. Reference [1] Wiland P, et al. Arthritis Rheumatol 2018;70(suppl 10). Disclosure of Interests Piotr Wiland Speakers bureau: Novartis, Pfizer, Abbvie, Gedeon-Richter, Lilly, Roche and Sandoz, Slawomir Jeka: None declared, Eva Dokoupilova: None declared, Juan Manuel Miranda Limon: None declared, Julia Jauch-Lembach Employee of: Hexal AG, Anjali Thakur Employee of: Hexal AG, Halimuniyazi Haliduola Employee of: Hexal AG, Norman Gaylis Grant/research support from: Multiple clinical research trials, BMS, AbbVie, GSK, Janssen, Amgen, Pfizer, Regeneron, UCB, Sanofi, SetPoint, ImmunPharma, Astra Zeneca, Sandoz, Novartis, Gilead, Consultant for: electroCore