Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study

Stanley Cohen, Mark C Genovese, Ernest Choy, Fernando Perez-Ruiz, Alan Matsumoto, Karel Pavelka, Jose L Pablos, Warren Rizzo, Pawel Hrycaj, Nan Zhang, William Shergy, Primal Kaur, Stanley Cohen, Mark C Genovese, Ernest Choy, Fernando Perez-Ruiz, Alan Matsumoto, Karel Pavelka, Jose L Pablos, Warren Rizzo, Pawel Hrycaj, Nan Zhang, William Shergy, Primal Kaur

Abstract

Objectives: ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab.

Methods: In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity.

Results: A total of 526 patients were randomised (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% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies.

Conclusions: 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.

Trial registration number: NCT01970475; Results.

Keywords: DMARDs (biologic); TNF-alpha; anti-TNF; inflammation; rheumatoid arthritis.

Conflict of interest statement

Competing interests: SC reports grants and personal fees from Amgen, during the conduct of the study; grants and personal fees from Abbvie, Boehringer Ingelheim, Pfizer and Sandoz, outside the submitted work. MCG reports grants and personal fees from Amgen, AbbVie and Pfizer, and personal fees from Sandoz, FKb, Samsung BioEpis, Merck, Celltrion and Boehringer, during the conduct of the study. EC reports grants and personal fees from Amgen, during the conduct of the study; personal fees from Boehringer Ingelheim, Chelsea Therapeutics, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hospita, ISIS, Jazz Pharmaceuticals, Janssen, MedImmune, Merrimack Pharmaceutical, Merck, Napp, Novartis, Regeneron, Sanofi-Aventis, Schering Plough, Synovate and Tonix and grants and personal fees from Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer, Pierre Fabre, Roche and UCB, outside the submitted work. FP-R reports grants from Amgen, during the conduct of the study; and personal fees from Amgen, outside the submitted work. AM reports grants and personal fees from Amgen, during the conduct of the study; grants and personal fees from AbbVie, Pfizer and Bristol-Myers Squibb, grants from Takeda, Janssen, Gilead and UCB and personal fees from GlaxoSmithKline, outside the submitted work. JLP reports lecturing and consultancy fees from Roche, Novartis, Pfizer and Lilly, outside the submitted work. NZ and PK are employees of Amgen Inc.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Patient disposition. *n=1 patient took prohibited concomitant medication due to an adverse event and was discontinued from the study. First patient was screened on 15 October 2013 and enrolled on 24 October 2013. Patients screened, n=747; per-protocol analysis set, n=463 (ABP 501, n=230; adalimumab, n=233).
Figure 2
Figure 2
(A) Percentage of patients achieving ACR20 by study week (full analysis set). ACR20, 20% improvement from baseline in American College of Rheumatology core set measurements. (B) Ratio of ACR responses at week 24. ACR20, 20% improvement from baseline in American College of Rheumatology core set measurements. RR, risk ratio; 95% CI 0.938, 1.152.
Figure 3
Figure 3
Mean±SD change from baseline in DAS28-CRP by study week (full analysis set). DAS28-CRP, Disease Activity Score 28-joint count-C reactive protein.
Figure 4
Figure 4
(A) Immunogenicity at any time point post-baseline throughout the study. (B) ACR20 responders by ADA status throughout the study (full analysis set). ACR20, 20% improvement from baseline in American College of Rheumatology core set measurements.

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