ACR Abstract Roundup: Pfizer and Celltrion Agents Demonstrate Safety, Efficacy

Biosimilar developments reported at the American College of Rheumatology (ACR) Convergence 2020 virtual meeting included data from safety and efficacy trials for Pfizer and Celltrion versions of adalimumab.

PF-06410293

Positive safety, immunogenicity and efficacy findings were reported for the Pfizer adalimumab biosimilar PF-06410293 (Abrilada, ADL-PF) in a study of patients with moderate-to-severe active rheumatoid arthritis (RA).¹

In an earlier study, ADL-PF, which has been approved in the United States and European Union, was compared with reference adalimumab sourced from the European Union (ADL-EU) and demonstrated therapeutic equivalence in patients with active RA. Comparable safety, efficacy, and immunogenicity was maintained up to week 56, and no differences in outcomes were observed for patients who underwent a blinded switch to ADL-PF at week 26.

At the ACR Convergence 2020, updated findings were presented for weeks 52 to 92 in patients who continued ADL-PF (N = 552). At week 52, all patients remaining on ADL-EU were switched to ADL-PF. Investigators said efficacy response rates at week 78 were 84.2% for all patients, and 83.4%, 85.8%, and 84.3% for the biosimilar, week 26 switch, and week 52 switch groups, respectively.

Investigators said response rates according to the ACR20 scale, which defines positive change as a 20% improvement in a core set of measures, were comparable across the 3 groups.

On safety, investigators said ADL-PF was generally well tolerated across groups with comparable safety profiles. With regard to immunogenicity, investigators reported comparable rates of antidrug antibodies (ADAs) and neutralizing ADAs.

CT-P17

In a separate study presented at ACR Convergence 2020, investigators demonstrated efficacy and safety equivalence of the adalimumab biosimilar candidate CT-P17 to reference adalimumab in patients with moderate-to-severe active RA.²

CT-P17 is a high concentration (100 mg/mL), citrate-free formulation of the reference product. Investigators sought to show equivalence by efficacy at week 24 and by pharmacokinetics and overall safety over the first 24 weeks of administration.

Investigators randomized 648 patients 1:1 to reference and biosimilar adalimumab. They found that the ACR20 response rate at week 24 was 82.72% in both groups. Confidence intervals for treatment difference were fully within parameters set by the European Medicines Agency and the FDA. Secondary efficacy end points also were similar between cohorts.

Investigators noted a slightly higher serum trough concentration in patients receiving CT-P17 vs reference adalimumab at week 24: 5.3 μg/mL vs 4.3 μg/mL (P = .0501), respectively.

Safety profiles between groups also were similar. Most events were grade 1/2. Among the CT-P17 cohort (n = 324), there were 5 treatment-emergent adverse events leading to study discontinuation, vs 8 for the reference group (n = 324). Events leading to discontinuation considered related to the adalimumab treatment were 2 vs 4, respectively.

The number of patients who developed ADAs was lower at week 24 for those on CT-P17 vs reference (32.3% vs 35.8%, respectively). Among patients receiving CT-P17, 83 (25.6%) had neutralizing ADAs, vs 103 (31.8%) receiving reference product.

In March 2020, Celltrion applied for CT-P17 marketing authorization in the United States and Europe. Those applications are still pending.

References

1. Fleischmann R, Alvarez D, Bock A, et al. A randomized, double-blind phase 3 study comparing the efficacy, safety and immunogenicity of PF-06410293 (Abrilada™), an adalimumab (ADL) biosimilar, and reference ADL (Humira®) in patients with moderate to severe active RA: results from weeks 52-92. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0798.

2. Kay J, Jaworski J, Wojciechowski R, et al. A randomized, double-blind, phase 3 study to compare the efficacy and safety of a proposed high concentration (100 mg/mL) adalimumab biosimilar (CT-P17) with reference adalimumab in patients with moderate-to-severe active rheumatoid arthritis. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0800.