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

Stanley Cohen, Jose L Pablos, Karel Pavelka, Gerard Anton Müller, Alan Matsumoto, Alan Kivitz, Hui Wang, Eswar Krishnan, Stanley Cohen, Jose L Pablos, Karel Pavelka, Gerard Anton Müller, Alan Matsumoto, Alan Kivitz, Hui Wang, Eswar Krishnan

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.

Keywords: ABP 501; Adalimumab; Biosimilar; Efficacy; Long-term safety; Rheumatoid arthritis.

Conflict of interest statement

Ethics approval and consent to participate

This study was conducted in compliance with Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines - including Title 21 Part 56 of the US Code of Federal Regulations (CFR) relating to IRBs/IECs and GCP as described in the US Food and Drug Administration (FDA) CFR (21 CFR § 50, 56, 312) in accordance with applicable ICH regulations regarding clinical safety data management (E2A, E2B [R3]), European Community directives 2001/20, 2001/83, 2003/94 and 2005/28 as enacted into local law, and with ICH guidelines regarding scientific integrity (E4, E8, E9, and E10). In addition, this study was conducted in adherence to all local regulatory requirements, and requirements for data protection.

Consent for publication

Not applicable.

Competing interests

Stanley Cohen is a consultant and investigator at Amgen, Abbvie, Boehringer Ingelheim, Coherus, Merck, Pfizer, and Sandoz.

José Luis Pablos received honoraria for lectures and consultations from the following companies: BMS, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, and Sanofi, and is also an investigator at Amgen.

Karel Pavelka received honoraria for lectures and consultations from the following companies: AbbVie, Amgen, Biogen, BMS, MSD, Pfizer, Roche, and UCB.

Gerard Anton Müller is an investigator at Amgen.

Alan Matsumoto is a consultant and investigator at Amgen, Abbvie, Pfizer, and Takeda.

Alan Kivitz is a consultant and part of the speakers’ bureau at Amgen, Abbvie, Pfizer, UCB, Merck, and Sanofi-Regeneron.

Hui Wang is an employee and stockholder at Amgen.

Eswar Krishnan is an employee and stockholder at Amgen (at the time this work was done).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a Study design. b Patient disposition
Fig. 2
Fig. 2
Efficacy: a ACR20 response rate; b DAS28-CRP change from the baseline of the parent study

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