An open-label extension study to demonstrate long-term safety and efficacy of ABP 501 in patients with rheumatoid arthritis

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Abstract

Background

ABP 501 was evaluated in a phase 3 single-arm, open-label extension (OLE) study to collect additional safety and efficacy data in patients with rheumatoid arthritis (RA).

Methods

Subjects completing the final visit in the parent phase 3 randomized, double-blind, controlled equivalence study comparing the efficacy and safety of the biosimilar ABP 501 with adalimumab reference product (RP) were enrolled in this open-label extension (OLE) study. All subjects received 40 mg ABP 501 every other week for 68 weeks. Key safety endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and anti-drug antibody (ADA) incidences. Efficacy endpoints included ACR20 (at least 20% improvement in American College of Rheumatology core set measurements from baseline) and Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) change from baseline.

Results

Among 466/467 patients treated with ABP 501, 229 transitioned from the ABP 501 arm of the parent study (ABP 501/ABP 501) and 237 from the adalimumab RP arm (RP/ABP 501); 412/467 (88.2%) patients completed the study. The overall TEAE incidence was 63.7% (297/466); grade ≥ 3 TEAE incidence was 9.0% (42/466). The incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). The SAE incidence was 9.9% (46/466). Overall, 18.2% (85/466) of subjects developed binding ADAs and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The ACR20 response rate was 73.3% (340/464 subjects) at OLE baseline, and 78.8% (327/415 subjects) at week 70 of the OLE study. The overall mean DAS28-CRP change from the parent study baseline was − 2.25 at the OLE study baseline ( n = 440), − 2.36 at week 4 ( n = 463), − 2.41 at week 24 ( n = 450), − 2.55 at week 48 ( n = 433), and − 2.60 at week 70 ( n = 412). Efficacy was maintained throughout the study.

Conclusions

Efficacy previously demonstrated in the parent study was maintained in this OLE study with no new safety findings. Long-term safety, immunogenicity, and efficacy were similar in the ABP 501/ABP 501 and RP/ABP 501 groups. The single switch from RP to ABP 501 did not impact immunogenicity.

Trial registration

ClinicalTrial.gov, NCT02114931

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Most cited references 13

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Biosimilar Cost Savings in the United States: Initial Experience and Future Potential.

Andrew W Mulcahy, Jakub Hlavka, Spencer Case (2018)

The Biologics Price Competition and Innovation Act (BPCIA), enacted as part of the 2010 Patient Protection and Affordable Care Act (ACA), authorized the U.S. Food and Drug Administration (FDA) to create a new regulatory approval pathway for biosimilars, which are biologic drugs that are very similar to already approved "reference" biologics in terms of potency, safety, and efficacy, but are manufactured by different companies. In the seven years since the ACA, many drug manufacturers worked to push new biosimilars through development and FDA review. As of July 2017, there were three marketed biosimilars and two more that were approved by the FDA but not yet marketed. BPCIA's shorter, lower-cost biosimilar approval pathway was designed to introduce competition among biologic manufacturers. This article estimates potential future savings from biosimilars in the United States, summarizes the experience to date with the first marketed biosimilar in the United States, and discusses key policy issues surrounding biosimilars. We estimate that biosimilars will reduce direct spending on biologic drugs by $54 billion from 2017 to 2026, or about 3 percent of total estimated biologic spending over the same period, with a range of $24 to $150 billion. While our estimate uses recent data and transparent assumptions, we caution that actual savings will hinge on industry and regulatory decisions as well as potential policy changes to strengthen the biosimilar market.

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Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab

Jennifer Liu, Tamer Eris, Cynthia Li … (2016)

Background ABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed. Objective The objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods. Methods Comprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation. Results ABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions. Conclusion Based on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.

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Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab

Jyoti Velayudhan, Yuh-feng Chen, Amanda Rohrbach … (2016)

Background Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity. Objective A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity. Methods The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. Results The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities. Conclusion Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.

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Author and article information

Contributors

Stanley Cohen: 214-540-0700 , SCohen@dfwra.com , SCohen@arthdocs.com

Jose L. Pablos: jlpablos2@gmail.com

Karel Pavelka: pavelka@revma.cz

Gerard Anton Müller: gmueller@med.uni-goettingen.de

Alan Matsumoto: akmatsumoto@arapc.com

Hui Wang: hwang01@amgen.com

Eswar Krishnan: e.krishnan@hotmail.com

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 29 March 2019

Publication date PMC-release: 29 March 2019

Publication date (Print): 2019

Volume: 21

Electronic Location Identifier: 84

Affiliations

[1 ]GRID grid.477482.a, Internal Medicine, Rheumatology Division, , Metroplex Clinical Research Center, ; 8144 Walnut Hill Lane, Suite 800, Dallas, TX 75231 USA

[2 ]ISNI 0000 0001 1945 5329, GRID grid.144756.5, Instituto de Investigación Hospital 12 de Octubre, ; Madrid, Spain

[3 ]ISNI 0000 0000 8694 9225, GRID grid.418965.7, Institute of Rheumatology, ; Prague 2, Czech Republic

[4 ]Abteilung.für Nephrologie und Rheumatologie, Göttingen, Germany

[5 ]GRID grid.490547.b, Arthritis and Rheumatism Associates, ; Wheaton, MD USA

[6 ]Abteilung für Nephrologie und Rheumatologie, Göttingen, Germany

[7 ]ISNI 0000 0001 0657 5612, GRID grid.417886.4, Biosimilars Development, Amgen Inc., ; Thousand Oaks, CA USA

Article

Publisher ID: 1857

DOI: 10.1186/s13075-019-1857-3

PMC ID: 6440148

PubMed ID: 30922373

SO-VID: 8613ee84-211b-47b1-8527-12b53b93ed1e

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 31 August 2018

Date accepted : 4 March 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100002429, Amgen;

Award ID: n/a

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: abp 501,adalimumab,rheumatoid arthritis,long-term safety,efficacy,biosimilar

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ScienceOpen disciplines: Orthopedics

Keywords: abp 501, adalimumab, rheumatoid arthritis, long-term safety, efficacy, biosimilar

An open-label extension study to demonstrate long-term safety and efficacy of ABP 501 in patients with rheumatoid arthritis

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Most cited references 13

Biosimilar Cost Savings in the United States: Initial Experience and Future Potential.

Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab

Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab

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