Multi-Biomarker Test Reads Out Positive in 2 Pfizer-Sponsored Studies

Both studies involved Pfizer biosimilars and were sponsored by Pfizer. Infliximab Study. In the first study, patients were randomized to treatment with …

Investigators have presented evidence of what they say are successful, first-time tests of a multi-biomarker disease activity (MBDA) score in patients with rheumatoid arthritis (RA). Separate comparative studies of infliximab and adalimumab biosimilars vs their reference counterparts were presented at the American College of Rheumatology (ACR) Convergence 2020 meeting.

The value of the MBDA score (Vectra) is that it consists of measures of 12 serum proteins and is highly sensitive, thereby offering an alternative to “subjective” clinical observation of patient progress, they explained.

“Comparison of MBDA scores between treatment groups may provide additional evidence of biosimilarity using an objective, quantitative assessment of disease activity that is independent of the potential subjectivity of joint counts or patient or physician global assessments,” said Jonathan Kay, MD, of the University of Massachusetts Medical School, who served as lead investigator for both studies.

Both studies involved Pfizer biosimilars and were sponsored by Pfizer.

Infliximab Study

In the first study, patients were randomized to treatment with an infliximab biosimilar (Ixifi) vs reference infliximab (Remicade) sourced from the European Union.1

Investigators enrolled 650 patients who met 2010 ACR/EULAR disease classification criteria and had ≥ 4 months of RA duration. They received 3 mg/kg of infliximab intravenously at weeks 0, 2, 6 and then every 8 weeks, in combination with methotrexate (MTX). MBDA scores were on a scale of 1 to 100, with 100 being the highest level of disease activity. They reported initial treatment period activity for weeks 0 to 30.

Baseline mean scores for patients receiving the infliximab biosimilar were 61.3 vs 58.8 for the reference product. For the overall population, the mean scores at 30 weeks were 46.9 for both biosimilar and reference groups.

The proportions of patients with high MBDA scores at baseline in both the biosimilar and reference cohorts were similar: 66.0% vs 66.9%, respectively. At week 30, the proportions of patients with high MBDA scores decreased to 42.3% and 40.2%, respectively.

Investigators said the decreases in individual serum biomarker levels that formed the composite MBDA score also were similar between biosimilar and reference groups. They identified 3 biomarkers for which this was true—serum amyloid A, tumor necrosis factor receptor 1, and VEGF-A—but they said it held true also for other biomarkers included in the MBDA score.

Mean MBDA scores decreased 15.2 and 14.1 points, respectively from baseline to week 6 in the 2 groups, and disease stability between cohorts was noted through week 30.

Adalimumab Study

In the second study, investigators enrolled 597 patients with RA by 2010/EULAR criteria and disease duration of ≥ 4 months. They were randomized to adalimumab biosimilar (Abrilada) or European Union–sourced adalimumab reference product and received 40 mg subcutaneously every other week, in combination with MTX.2

Mean MBDA scores were calculated at baseline and weeks 6, 12, and 26. At baseline, the mean MBDA scores for the biosimilar and reference groups were 57.2 and 58.3, respectively. “Mean values of MBDA scores were comparable between treatment groups at all measured time points through 26 weeks,” the investigators wrote.

The proportions of patients with high MBDA scores decreased to 45.5% and 41.7% at week 26. Mean MBDA scores dropped from baseline by 11.9 and 12.4 points, respectively, by week 6; by 11.7 and 12.4 points at week 12; and by 14.3 and 15.5 points at week 26, respectively. Again, individual serum biomarker levels tracked one another closely between biosimilar and reference cohorts.

The mean scores over the 26 weeks for both cohorts were similar, leading adalimumab investigators to conclude: “MBDA score based on 12 serum biomarkers provides a sensitive and objective clinical assessment of biosimilarity that does not require physical examination of the patient or subjective patient global assessment of DA.”

References

1. Kay J, alvarez D, Rehman MI, Zhang M, Iikuni N. Use of multi-biomarker disease activity scores to assess biosimilarity in a phase 3, randomized controlled trial comparing biosimilar infliximab-qbtx (PF-06438179/GP1111) with EU-sourced reference infliximab in patients with active RA. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1204.

2. Kay J, Bock A, Iikuni N, Zhang W, Alvarez D. Use of multi-biomarker disease activity scores to compare biosimilar adalimumab-afzb (PF-06410293) with EU-sourced reference adalimumab in a phase 3, randomized, double-blind trial in patients with active RA. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1233.