The clinical trials used to support the approval of Samsung Bioepis/Merck’s adalimumab biosimilar SB5 (Imraldi/Hadlima), were critically reviewed by authors from Argentina and the UK, with a special focus on rheumatoid arthritis (RA) [1].
Imraldi was approved in Europe in August 2017 [2] and Hadlima (adalimumab-bwwd) was approved in the US in July 2019 [3].
Biosimilar approval does not require the manufacturer to re-establish efficacy but is instead based on the demonstration that there are no clinically meaningful differences from the reference product [4, 5].
Samsung Bioepis/Merck demonstrated that SB5 and the reference product (Humira) were highly similar in terms of analytical structure, function and pharmacokinetics (PK). The phase I PK study (NCT02144714) was carried out in 189 healthy subjects after a single 40 mg subcutaneous injection and demonstrated PK similarity, as well as similar safety and tolerability [6]. A phase III study was then carried out in RA (NCT02167139).
The phase III RA study (NCT02167139) was a randomized, double-blind, parallel-arm, active comparator-controlled, 52-week equivalence study in 544 patients with moderate to severe active RA despite methotrexate therapy. During the study, patients were randomized to SB5, EU-sourced Humira or US-sourced Humira (40 mg subcutaneous) every 2 weeks. At Week 24, patients on Humira were re-randomized to SB5 or Humira until Week 52.
ACR20* and ACR50 response at Week 52 showed a trend of superior response in both SB5 and SB5/Humira-switch groups compared to the Humira group, using the per-protocol set (upper limit of CI: 15.9%, exceeding ±15%) but not using the full analysis set. The percentage of subjects who achieved major clinical response (ACR70 for 6 consecutive months) at Week 52 was 15.7% in the SB5 group, 15.3% in the switch group and 9.7% in the Humira group. Since the study was not designed to show similarity at Week 52, these findings were not considered as superior response. Other response measures (ACR50/70, DAS28**) were similar. Samsung Bioepis also reported that at Week 24, the ACR20 improvement from baseline was within the pre-specified equivalence margin for SB5 compared to Humira, leading the company to conclude that the biosimilar is ‘clinically equivalent’ to Humira [7].
The incidence of anti-drug antibodies (ADAs) was similar between SB5 and Humira groups (33.1 vs 32.0% up to Week 24, respectively). Overall, treatment emergent adverse events (AEs) occurred in 35.8% of the SB5 and 40.7% of the Humira group; 10.1 and 11.7%, respectively, were considered related to the study drug. The number of injection site reactions was higher in Humira recipients (32 reactions in 4 patients) compared to SB5 recipients (9 reactions in 8 patients) at Week 52, although the proportions of patients were comparable (3.1 vs 3.0%, respectively). The rate of discontinuation due to AEs was lower in the SB5 than in the Humira group (0.7 vs 3.3% at Week 24; 1.5 vs 2.4% at Week 52).
*The ACR20 is the American College of Rheumatology criteria for clinical improvement in patients with rheumatoid arthritis, indicating a 20% improvement across a series of diagnostic parameters.
**Disease Activity Score-28 for rheumatoid arthritis with C-Reactive Protein.
Related articles
Clinical trials for adalimumab biosimilar BI 695501
Clinical trials for adalimumab biosimilar ABP 501
Clinical trials supporting the approval of adalimumab biosimilars
Biosimilars of adalimumab
References
1. Zhao S, Chadwick L, Mysler E, Moots RJ. Review of Biosimilar Trials and Data on Adalimumab in Rheumatoid Arthritis. Curr Rheumatol Rep. 2018;20(10):57.
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
3. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US
4. GaBI Online - Generics and Biosimilars Initiative. EU guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Guidelines/EU-guidelines-for-biosimilars
5. GaBI Online - Generics and Biosimilars Initiative. US guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Guidelines/US-guidelines-for-biosimilars
6. GaBI Online - Generics and Biosimilars Initiative. Phase I results for candidate adalimumab, etanercept and infliximab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Biosimilars/Research/Phase-I-results-for-candidate-adalimumab-etanercept-and-infliximab-biosimilars
7. GaBI Online - Generics and Biosimilars Initiative. Phase III results of adalimumab biosimilar demonstrate equivalence [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 4]. Available from: www.gabionline.net/Biosimilars/Research/Phase-III-results-of-adalimumab-biosimilar-demonstrate-equivalence
Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.
Copyright – Unless otherwise stated all contents of this website are © 2020 Pro Pharma Communications International. All Rights Reserved.
0
Post your comment