At ACR, New Data for Amgen's Proposed Infliximab and Rituximab Biosimilars in RA

In December 2018, biosimilar developer Amgen announced that it had submitted its proposed infliximab biosimilar, ABP 710, referencing Remicade, to the FDA for review. A regulatory decision is expected soon, and on Sunday, during the American College of Rheumatology (ACR)’s 2019 meeting, being held in Atlanta, Georgia, researchers reported on the safety and efficacy of the proposed infliximab biosimilar in a phase 3 study of patients with rheumatoid arthritis (RA).

ABP 710

In the multicenter, randomized, double-blind, active-controlled, multiple-dose study, the biosimilar was compared with the reference infliximab.¹ In total, 556 patients were treated with the biosimilar (n = 278) or the reference (n = 278) at a dose of 3 mg/kg on day 1 and at weeks 2 and 6, then every 8 weeks until week 22. The primary end point of the study was response difference in terms of the ACR criteria for 20% improvement (ACR20) at week 22.

Patients who completed the 22 weeks who were initially given the reference drug were randomized to continue treatment with the reference (n = 121) or switch to the biosimilar (n = 119) and receive treatment until week 46; patients randomized to the biosimilar continued their therapy (n = 244) until week 46.

The response difference in terms of ACR20 at week 22 was 9.37 (90% CI, 2.67-15.96), and, write the authors, results of the ACR20, ACR50, and ACR70 response rates across groups were similar, with overlapping 95% CIs of ACR response rates between groups at all and with narrow response differences at all time points.

An additional analysis presented by the same research team showed that, the ACR components that had the largest response difference between treatment groups were Subject’s Assessment of Disease-related Pain (—30.8; standard deviation [SD], 28.75) and Health Assessment Questionnaire Disability Index (–0.53; SD, 0.59) scores.² The difference in mean change from baseline and the associated 90% and 95% CIs were below the thresholds of minimal clinically important improvement, however, and so were not deemed clinically meaningful.

ABP 798

On Sunday, researchers also reported on a phase 1 and 3 study of the proposed rituximab biosimilar, ABP 798, in patients with RA.³ Positive topline results from the study were first announced in January of this year, and the data presented on Sunday from the randomized, double-blind, active-controlled study give a further look at the safety and efficacy of this proposed therapy in the setting of RA.

The study, which had a primary efficacy end point of change in baseline at week 24 in disease activity score in a count of 28 joints with C-reactive protein (DAS28-CRP), included 311 patients with RA who had not achieved an adequate response to disease-modifying therapies. Patients were randomized to receive 2 intravenous infusions of 1000 mg of the biosimilar (n = 104), the EU-licensed reference (n = 104), or the US-licensed reference (n = 103) 2 weeks apart. At week 24, those receiving the biosimilar or the EU reference received another dose of their therapy, while those on the US reference switched to the biosimilar.

In terms of change from baseline in terms of DAS28-CRP, the 90% CI (—0.225 to 0.264) and 95% CI (–0.273 to 0.312) fell within the prespecified equivalence margin of –0.6 to 0.6, thereby demonstrating clinical equivalence between the biosimilar and the reference products. The 90% and 95% CIs for the mean differences between the biosimilar and the EU and US arms taken individually were also within the prespecified margin.

Treatment-emergent adverse events (AEs) were reported in 50% of the biosimilar arm, 42.3% of the EU reference arm, and 42.7% of the US reference arm. Infusion-related reactions were the most common AEs of interest. Binding antibodies and neutralizing antibodies, respectively developed in 13.4% and 8.2% of the biosimilar arm, 10.6% and 2.1% of the EU reference arm, and 10.6% and 8.2% of the US reference arm.

Based on these results, say the authors, the clinical equivalence of the biosimilar to the EU and US references has been established.

References

1. Genovese M, Sanchez-Burson J, Balázs É, Everding A, Oh MS, Fanjiang G, Cohen S. Efficacy and safety results from a phase 3 study of biosimilar candidate ABP 710 in subjects with moderate to severe RA. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, Georgia. Abstract 520.

2. Genovese M, Sanchez-Burson J, Balázs É, Everding A, Oh MS, Fanjiang G, Cohen S. Efficacy of biosimilar candidate ABP 710 in a phase 3 study in subjects with moderate to severe RA: additional analysis focusing on the ACR individual components. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, Georgia. Abstract 519.

3. Burmester G, Drescher E, Hrycaj P, Chien D, Pan Z, Cohen S. Efficacy and safety results from a randomized double-blind study that compared the proposed biosimilar ABP 798 with rituximab in subject with moderate to severe RA. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, Georgia. Abstract 537.