Sandoz, the generics division of Novartis, announced on 15 June 2018 results of new phase III, long-term and switching data for its infliximab biosimilar Zessly (PF‑06438179) and its etanercept biosimilar Erelzi in rheumatoid arthritis patients.
Results from the 54-week REFLECTIONS B537‑02 study of Zessly and the 48-week EQUIRA study of Erelzi showed, according to Sandoz, that each biosimilar matched its reference biological in terms of safety, efficacy and quality, reinforcing previously presented findings. The research also indicated that switching from the reference medicine to the biosimilar did not affect safety, efficacy or immunogenicity [1, 2].
REFLECTIONS B537‑02 is a phase III, double-blind, parallel-group, confirmatory study of Zessly versus the originator biological Remicade (infliximab) in combination with methotrexate in 650 biological-naïve, adult patients with moderately to severely active rheumatoid arthritis who had an inadequate response to methotrexate therapy alone.
The study met its primary endpoint, demonstrating equivalent efficacy of Zessly to the reference medicine as measured by the American College of Rheumatology 20 (ACR20) response at Week 14. The research demonstrated that there were no clinically meaningful differences from 30 to 54 weeks in terms of safety, efficacy and immunogenicity between patients with rheumatoid arthritis remaining on biosimilar and reference infliximab. The same results were found when patients on reference infliximab were blindly re-randomized to switch to biosimilar infliximab or remained on reference therapy [1].
Patients were on a stable dose of methotrexate at initiation of treatment and randomized 1:1 to Sandoz infliximab (n = 324) or reference infliximab (n = 326) at a dose of 3 mg/kg IV at Weeks 0, 2, 6, and then every 8 weeks, with one dose escalation to 5 mg/kg allowed at or after week 14 for inadequate responders for 30 weeks. At Week 30, 566 patients entered the second treatment phase and 280 patients continued onto treatment with Zessly. At Week 30, patients (n = 286) were blindly re-randomized (1:1) to remain on treatment (n = 143) or switch to Zessly (n = 143) [1].
Incidence of adverse events (AEs) were comparable among the Zessly and Remicade and switched treatment groups. Overall, post-dose anti-drug antibody (ADA) rates were comparable among the groups (52.1%, 60.1%, and 58.0%, respectively) [1].
EQUIRA was a 48-week, randomized, double-blind, phase III study that compared the efficacy and safety of Erelzi versus originator etanercept Enbrel in 376 adults with moderate to severe rheumatoid arthritis. The study also evaluated the effects of switching from Enbrel to Erelzi [6].
This new research demonstrated that switching rheumatoid arthritis patients from Enbrel to Erelzi does not affect the overall therapy outcome in terms of efficacy, safety and immunogenicity [2].
A total of 376 patients with active rheumatoid arthritis and inadequate response to methotrexate were randomized 1:1 to 50 mg Erelzi or Enbrel subcutaneously once weekly for 24 weeks, at which point the primary endpoint for equivalence (change from baseline in DAS28-CRP at Week 24) was met. Patients with at least moderate response at Week 24 either continued Erelzi treatment or, in the Enbrel group, were switched to receive 50 mg Erelzi up to 48 weeks [2].
At Week 48, the EULAR and ACR 20/50/70 response rates were comparable between the two groups. Following Week 24, treatment-emergent AEs occurred in 42.9% vs 38.0% patients in the continued Sandoz etanercept (n = 175) versus the switched (n = 166) groups; serious AEs occurred in 2.3% versus 2.4% patients. The mean change in DAS28-CRP from baseline to Week 48 was comparable between the group that continued and the group that switched to Erelzi [2].
These data were presented at the European League Against Rheumatism (EULAR) 2018 Annual Meeting, which was held on 13−16 June 2018 in Amsterdam, The Netherlands.
Erelzi and Zessly were approved in Europe in June 2017 [3] and May 2018 [4], respectively. Erelzi was also approved in the US in August 2016 [5].
Conflict of interest
Several of the authors of the abstracts [1, 2] reported conflicts of interest, including having received grant/research support from, having acted as a consultant for or being an employee of various 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 preliminary until published in a peer-reviewed journal.
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References
1. Alten R, Tseluyko V, Hala T, et al. FRI0137: Efficacy, safety and immunogenicity from week 30 to week 54 in a randomised, double-blind phase iii study comparing a proposed infliximab biosimilar (PF-06438179/GP1111) with reference infliximab. European League Against Rheumatism (EULAR) 2018 Annual Meeting; 13−16 June 2018; Amsterdam, The Netherlands.
2. Matucci-Cerinic M, Schulze-Koops H, Buch M, et al. FRI0129: Switch between reference etanercept (ETN) and gp2015, an etanercept biosimilar, did not impact efficacy and safety in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase 3 equira study. European League Against Rheumatism (EULAR) 2018 Annual Meeting; 13−16 June 2018; Amsterdam, The Netherlands.
3. GaBI Online - Generics and Biosimilars Initiative. EC approval for etanercept biosimilar Erelzi [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 31]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-etanercept-biosimilar-Erelzi
4. GaBI Online - Generics and Biosimilars Initiative. EC approval for infliximab biosimilar Zessly [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 31]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-infliximab-biosimilar-Zessly
5. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 31]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US
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