Background/Purpose: To support a demonstration of interchangeability of proposed biosimilar AVT02 and Humira® (reference adalimumab).

Methods: Participants with chronic plaque psoriasis were selected for the study population. This population was judged to be adequately sensitive to detect pharmacokinetic (PK) differences resulting from switching between reference adalimumab and AVT02, as well as differences in common adverse events and immunogenicity. This population was also considered the most sensitive to compare treatment efficacy. This study enrolled 567 participants. Following a 12-week open label lead-in-period when all participants received reference adalimumab, participants with Psoriasis Area Severity Index(PASI)75 response were randomized 1:1 to receive AVT02 alternating with reference adalimumab (switching arm) or reference adalimumab (non-switching arm). At Week 28, participants with PASI50 response could opt to take part in an open-label extension phase receiving AVT02 up to Week 50, with end-of-study follow up at Week 52 (Figure 1).

Intensive PK sampling was performed for both arms during final exposure in the switching module and AUC_{tau, W26-28} and C_{max, W26-28} were calculated. Additional PK parameters were assessed, as well as efficacy outcomes PASI score, static Physician’s Global Assessments (sPGA), and quality of life score, during the switching period. Serum concentration, safety, tolerability, and immunogenicity were assessed throughout the study.

Results: The 90% CIs for the switching vs the non-switching arm arithmetic mean ratios for AUC_tau,W26-28 and C_max,W26-28 were within the prespecified limits of 80% to 125%, demonstrating comparable PK profile between groups. Efficacy endpoints were also similar across both arms at Week 28.

The adverse event profile was comparable at Week 28, persisting to Week 52. Injection site reactions were reported by 2.5% of participants in the switching arm, and 5.5% in the non-switching arm during the switching module.

The time of onset and frequency of ADAs and NAbs were similar in participants in both switching (78.3% ADA+; 92.2% NAb+) and non-switching groups (76.4% ADA+; 91.0% NAb+) through Week 28. Immunogenicity profile persisted through Week 52.

Through Week 28, NAb+ participants had similar PASI score improvement and similar PK parameters in switching and non-switching groups. From Week 28 to Week 52, NAb+ participants had similar serum trough level compared with both arms in the switching module.

Conclusion: The PK similarity, similar efficacy endpoints,  comparable adverse event and ADA/NAb profiles  interchangeability between AVT02 and reference adalimumab. 

ClinicalTrials.gov Identifier: NCT04453137

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-clinical-study-designed-to-support-a-demonstration-of-interchangeability-between-avt02-and-reference-adalimumab-humira/