The clinical trials used to support the approval of Amgen’s ABP 501 (Amjevita/Amgevita/
Solymbic) were critically reviewed by authors from Argentina and the UK [1].
Amgevita/Solymbic were approved in Europe in March 2017 [2] and Amjevita (adalimumab-atto) was approved in the US in September 2016 [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].
Amgen demonstrated that ABP 501 and the reference product were highly similar in terms of analytical structure, biofunctional activity and pharmacokinetics (PK). The phase I PK study (EudraCT number 2012-000785-3) was carried out in healthy subjects after a single 40 mg subcutaneous injection and ‘demonstrated PK similarity’, as well as similar safety and tolerability. Subsequent phase III studies were carried out in both plaque psoriasis (NCT01970488) and rheumatoid arthritis (RA) (NCT01970475).
The psoriasis study (NCT01970488) was a 52-week, double-blind, randomized study in patients with moderate to severe psoriasis. At Week 16, those with 50% or more improvement in Psoriasis Area and Severity Index (PASI) score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were re-randomized to reference product (AbbVie’s Humira) or ABP 501. A total of 350 patients (175 per group) were enrolled and randomized.
The PASI improvement at Week 16 was 80.9% for ABP 501 and 83.1% for the Humira (least-square mean difference −2.18 [95% confidence interval −7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and anti-drug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs Humira were similar. Safety, including immunogenicity, was similar among groups after single transition (Week 20). These results, according to the authors showed that ABP 501 was ‘clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501)’.
The rheumatoid arthritis (RA) study (NCT01970475) was a randomized, double-blind, active comparator-controlled, 26-week equivalence study in patients with moderate to severe active RA despite methotrexate. During the study, patients were randomized (1:1) to ABP 501 or adalimumab (40 mg) every two weeks.
A total of 526 patients were randomized (n = 264, ABP 501; n = 262 adalimumab) and 494 completed the study. ACR20* response at Week 24 was 74.6% (ABP 501) and 72.4% (Humira). At Week 24, the risk ratio of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis that the treatments were equivalent. Changes from baseline in DAS28-CRP**, ACR50 and ACR70 were similar. There were no clinically meaningful differences in adverse events (AEs) and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding anti-drug antibodies. The authors concluded that the ‘results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA’.
*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.
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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 Apr 10]. 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 Apr 10]. 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 Apr 10]. 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 Apr 10]. Available from: www.gabionline.net/Guidelines/US-guidelines-for-biosimilars
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