No Safety Risks Found in a Switch From Reference Rituximab to GP2013

GP2013, a biosimilar rituximab developed by Sandoz and licensed in the European Union under the brand names Rixathon and Riximyo, is used to treat both malignant and inflammatory diseases. A recently published paper, appearing in Arthritis Care and Research, says that researchers detected no safety risks when switching patients with rheumatoid arthritis (RA) from reference rituximab (Rituxan) to the biosimilar.

The paper¹ reports on findings from the randomized, double-blind, controlled study that were first presented² in abstract form at the American College of Rheumatology's 2017 meeting. The 107 patients enrolled in the study were adults with RA who had previously received the reference rituximab as part of routine care.

Notably, there was no limitation regarding the duration of patients’ previous rituximab treatment. According to the authors, this is the first randomized switching study in patients who had previously received the reference that did not impose such a limitation.

After screening and evaluation for antidrug antibodies (ADAs), the patients were randomized to receive either 2 infusions of the reference product (n = 54), sourced from either the United States or European Union, or the biosimilar (n = 53) together with a stable dose of methotrexate.

The incidence of 3 types of reactions comprised the assessment of adverse events (AEs) that could be associated with the switch: anaphylactic reactions, hypersensitivity, and infusion-related reactions (IRRs).

Only 1 patient (in the reference group) experienced anaphylaxis during the study. From the first infusion to the end of the study, 5 patients in the biosimilar group and 6 patients in the reference group experienced hypersensitivity; 6 patients in the biosimilar group and 10 patients in the reference group experienced IRRs.

ADAs were detected in only 1 patient (in the reference group). The 2 patients who tested positive for ADAs at screening both tested negative at all later time points.

AEs were reported by 37 patients in the biosimilar group and 28 patients in the reference group, but more patients in the reference group (n = 3) reported severe AEs than in the biosimilar group (n = 1).

The authors concluded that no safety risks were detected when patients switched from the reference to the biosimilar and that the safety profiles of patients in both groups were similar.

While the study’s results are welcome news for European patients who may be switched to the cost-saving biosimilar, US patients continue to wait for a biosimilar rituximab option to treat RA; in November 2018, Sandoz announced that it would no longer pursue FDA approval for the drug after having received a May 2018 Complete Response Letter. The company said at the time that it believed that US marketplace needs would be satisfied by other products before it could generate the data requested by the FDA for the drug’s US approval.

However, the 1 FDA-approved biosimilar rituximab, Celltrion and Teva’s Truxima, does not carry an indication for RA, as it was approved in only oncology indications. The drug makers indicated that their decision not to seek approval for the drug in inflammatory diseases was related to intellectual property issues.

References

1. Tony HP, Krüger K, Cohen SB, et al. Safety and immunogenicity of rituximab biosimilar GP2013 after switch from reference rituximab in patients with active rheumatoid arthritis. Arthritis Care Res. 2019;71(1):88-94. doi: 10.1002/acr.23771.

2. Tony HP, Schulze-Koops H, Kruger K, et al. Presented at the American College of Rheumatology 2017 Meeting; November 7, 2017; San Diego, CA. Abstract 2795. acrabstracts.org/abstract/comparison-of-switching-from-the-originator-rituximab-to-the-biosimilar-rituximab-gp2013-or-re‑treatment-with-the-originator-rituximab-in-patients-with-active-rheumatoid-arthritis-safety-and.