On 23 October 2018, Sandoz, the generics division of Novartis, presented positive phase III data for its adalimumab and etanercept biosimilars [1, 2].
The phase III adalimumab study compared the efficacy and safety of Sandoz’s adalimumab biosimilar, GP2017, and reference adalimumab (refADL) in patients with moderate-to-severe rheumatoid arthritis (RA) with inadequate response to disease modifying anti-rheumatic drugs, including methotrexate.
The study, which was completed in September 2017, enrolled 353 eligible patients and randomized them 1:1 to receive 40 mg of GP2017 (n = 177) or refADL (n = 176) subcutaneously every other week from Week 0 to Week 22. The mean change in Disease Activity Score for 28 joints – C-Reactive Protein (DAS28-CRP) from baseline at Week 12 was -2.16 for GP2017 (n = 140) and -2.18 for refADL (n = 144) (∆ = 0.02; 95% CI: -0.24,0.27). Treatment-emergent adverse events (TEAEs) occurred in 61.6% of patients in the GP2017 group and 60.2% of patients in the refADL group. Most TEAEs were mild or moderate in severity. Anti-drug antibodies were detected in 21.8% and 24.4% of patients treated with GP2017 and refADL, respectively, of which >70% in both groups were neutralizing.
The authors concluded that ‘these data demonstrate equivalent efficacy of proposed adalimumab biosimilar GP2017 and refADL in patients with moderate-to-severe RA’. They added that the ‘safety and immunogenicity of GP2017 and refADL were similar and consistent with clinical experience with refADL’.
In addition, phase III data from the EQUIRA trial, which was completed in June 2017, were presented. The 48-week, randomized, double-blind, phase III, two treatment period confirmatory study compared the change from baseline in DAS28-CRP at Week 24.
A total of 376 patients ≥18 years with active RA (ACR 1987 or ACR/EULAR 2010 criteria for ≥ 6 months before baseline and active disease defined as DAS28-CRP ≥ 3.2 and CRP > 5 mg/L or ESR ≥28 mm/h) and inadequate response to methotrexate (MTX) were randomized 1:1 to receive 50 mg of GP2015 (n = 186) or originator etanercept (ETN) (n = 190) subcutaneously once weekly for 24 weeks (Treatment period 1 [TP1]). Patients with at least moderate EULAR response at Week 24 either continued GP2015 treatment or, in the ETN group, were switched to receive 50 mg GP2015 up to 48 weeks (Treatment period 2 [TP2]). All patients continued to receive concomitant MTX (10–25 mg/week) at a stable dose and folic acid.
The primary endpoint for equivalence during TP1 was met [3]. At Week 48, the American College of Rheumatology 20% improvement (ACR20) response rates were comparable between patients who continued on or switched to GP2015. In TP2, TEAEs occurred in 42.9% vs 38.0% patients with only 13.1% vs 11.4% considered drug related in the continued GP2015 (n = 175) vs the switched (n = 166) groups; serious adverse events occurred in 2.3% vs 2.4% patients (TP2 safety set). Injection site reactions occurred in 6 (3.6%) patients in the switched group but none in the continued GP2015 group. In TP2, 4 (2.4%) patients in the continued GP2015 group had single-event, very low titre, non-neutralizing anti-drug antibodies detected.
These data were presented at the American College of Rheumatology (ACR) 2018 Annual Meeting, which was held on 19−24 October 2018 in Chicago, IL, USA.
The adalimumab biosimilar (GP2017) was approved in Europe as Halimatoz, Hefiya and Hyrimoz (GP2017) in July 2018 [4] and by the US Food and Drug Administration (FDA) as Hyrimoz (GP2017) in October 2018 [5].
The etanercept biosimilar, Erelzi (GP2015), was approved by FDA in all five indications of the originator product (Enbrel) in August 2016 [6]. It was approved in Europe in June 2017 [7].
Conflict of interest
The authors of the abstracts [1, 2] reported conflict of interest, including being employees of pharmaceutical companies. For full details of the authors’ conflict of interest, see the abstracts [1, 2].
Editor’s comment
It should be noted that data of the studies presented in this article were published as abstracts and presented at a conference. These data and conclusions should be considered as preliminary until published in a peer-reviewed journal.
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Biosimilars of etanercept
References
1. Wiland P, Jeka S, Dokoupilová E, et al. A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Efficacy, Safety and Immunogenicity of a Proposed Adalimumab Biosimilar (GP2017) with Reference Adalimumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis. American College of Rheumatology (ACR) 2018 Annual Meeting; 19-24 October 2018; Chicago IL, USA. Abstract No. 1936.
2. Kavanaugh A, Matucci-Cerinic M, Schulze-Koops H, et al. Phase 3 Equira 48 Week Study Results Demonstrated No Impact on Efficacy and Safety When Patients with Moderate-to-Severe Rheumatoid Arthritis Were Switched between Reference Etanercept (ETN) and GP2015, an Etanercept Biosimilar. American College of Rheumatology (ACR) 2018 Annual Meeting; 19-24 October 2018; Chicago IL, USA. Abstract No. 2550.
3. GaBI Online - Generics and Biosimilars Initiative. Positive switching data for infliximab and etanercept biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Dec 14]. Available from: www.gabionline.net/Biosimilars/Research/Positive-switching-data-for-infliximab-and-etanercept-biosimilars
4. GaBI Online - Generics and Biosimilars Initiative. Adalimumab and trastuzumab biosimilars gain EC approval [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Dec 14]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-and-trastuzumab-biosimilars-gain-EC-approval
5. GaBI Online - Generics and Biosimilars Initiative. FDA approves adalimumab and pegfilgrastim biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Dec 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-adalimumab-and-pegfilgrastim-biosimilars
6. GaBI Online - Generics and Biosimilars Initiative. FDA approves biosimilar etanercept Erelzi [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Dec 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-biosimilar-etanercept-Erelzi
7. GaBI Online - Generics and Biosimilars Initiative. EC approval for etanercept biosimilar Erelzi [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Dec 14]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-etanercept-biosimilar-Erelzi
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